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Corticosteroids, a commonly prescribed medication to alleviate cancer-related symptoms for non-small cell lung cancer patients treated with immunotherapy, are the main reason certain immunotherapies may fail in treating the disease, according to new research by 

, showed that high doses of steroids, when given before and/or during a specific type of immunotherapy, caused patients’ tumors to shrink less than those of patients not on steroids. Those patients also did not live as long.

“Steroids were the biggest predictor of why certain immunotherapies may not be effective, even when considering multiple other factors such as stage and progression of the disease,” said Keck Medicine oncologist and immunologist 

Additionally, researchers believe they have found the mechanism behind why steroids and some immunotherapies may not mix.

“Our findings reveal that steroids stop the body’s natural cancer-fighting cells, T-cells, from maturing. This makes them unable to attack the cancer as vigorously as they usually would, leading to worse outcomes for patients,” said Ito, who is also a member and co-leader of the translational and clinical sciences research program at 

. “While other research has indicated steroids may negatively impact immunotherapy’s efficacy, we are one of the first to pinpoint a probable cause and effect.”

Ito and his colleagues also discovered that steroids blocked circulating biomarkers in the body — bits of cells in the bloodstream that signal when cancer is progressing so oncologists can adjust the patient’s treatment.

“Without the presence of circulating biomarkers to inform our decisions, oncologists cannot treat the cancer as effectively and patients may miss out on the best treatment for their cancer,” said Ito.

The study examined the effect of steroids on a type of immunotherapy known as immune checkpoint inhibitors (ICIs). ICIs help the body's immune system fight cancer by blocking proteins that prevent T-cells from attacking cancer cells. ICIs are often used to treat non-small cell lung cancer, the most common form of lung cancer. 

Steroids are often prescribed to alleviate symptoms of the cancer or treatments given for a variety of reasons, such as fatigue and vomiting, or more serious side effects like brain swelling and lung inflammation. Steroids suppress the immune system, which reduces the inflammation that can cause these conditions.

Ito and fellow researchers retrospectively studied the medical records of 277 patients with Stage II-IV non-small cell lung cancer who were treated with ICIs alone or in combination with other therapies. They compared outcomes (tumor shrinkage and survival rate) between patients prescribed steroids and those who were not at three centers, including 

They analyzed up to eight years of data to determine that steroids were the sole factor impeding the effectiveness of the immunotherapy.

They also determined that the T-cells of significant numbers of patients on steroids were not fully matured and launched a preclinical study using mice to observe the effects of steroids on ICI therapy in real time. This mouse model study led to the discovery that steroids given before/during immunotherapy inhibit T-cells from fully maturing.

While the Keck Medicine research indicates steroids can interfere with ICIs, Ito acknowledges that for some patients, steroids may be necessary to manage their cancer-related symptoms.

“We know that steroids will continue to play an important role in lung cancer care, but it is important to understand their potential limitations,” said Ito. “Each patient should talk to their oncologist to make sure they have the best possible care plan tailored to their specific needs.”

He hopes this research will lead to more studies examining the effect of steroids on immunotherapy so oncologists can make fully informed decisions that will best benefit their patients.

Other study authors include Keck Medicine medical oncologists 

The study was supported with grants from the National Cancer Institute, P30CA016056 (RPCCC), P30CA014089 (USC), K08CA197966, R01CA255240, R01CA272827 (F. Ito), R01CA188900, R01CA267690 (B.H. Segal) as well as the Department of Defense Lung Cancer Research Program and the Uehara Memorial Foundation.

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Recent research from Keck Medicine of USC highlights that corticosteroids, often used to manage symptoms in non-small cell lung cancer patients undergoing immunotherapy, may hinder the effectiveness of immune checkpoint inhibitors (ICIs). High doses of steroids were linked to reduced tumor shrinkage and shorter patient survival. The study identified that steroids prevent T-cells from maturing, impairing their cancer-fighting ability. Additionally, steroids block circulating biomarkers, complicating treatment adjustments. While steroids remain crucial for symptom management, understanding their limitations is vital for optimizing cancer care.

High doses of corticosteroids are likely the most significant factor in why some immunotherapies don’t work.


Common Medication for Lung Cancer Symptoms Found to Limit Effectiveness of Cancer Treatment

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A new study led by Keck Medicine of USC researchers may have uncovered an effective combination therapy for glioblastoma, a brain tumor diagnosis with few available effective treatments. According to the National Brain Tumor Society, the average survival for patients diagnosed with glioblastoma is eight months.

The study finds that using Tumor Treating Fields therapy (TTFields), which delivers targeted waves of electric fields directly into tumors to stop their growth and signal the body’s immune system to attack cancerous tumor cells, may extend survival among patients with glioblastoma, when combined with immunotherapy (pembrolizumab) and chemotherapy (temozolomide).

TTFields disrupt tumor growth using low-intensity, alternating electric fields that push and pull key structures inside tumor cells in continually shifting directions, making it difficult for the cells to multiply. Preventing tumor growth gives patients a better chance of successfully fighting the cancer. When used to treat glioblastoma, TTFields are delivered through a set of mesh electrodes that are strategically positioned on the scalp, generating fields at a precise frequency and intensity focused on the tumor. Patients wear the electrodes for approximately 18 hours a day.

Researchers observed that TTFields attract more tumor-fighting T cells, which are white blood cells that identify and attack cancer cells, into and around the glioblastoma. When followed by immunotherapy, these T cells stay active longer and are replaced by even stronger, more effective tumor-fighting T cells.

“By using TTFields with immunotherapy, we prime the body to mount an attack on the cancer, which enables the immunotherapy to have a meaningful effect in ways that it could not before,” said 

, chief of neuro-oncology with Keck Medicine, co-director of the 

 and corresponding author of the study. “Our findings suggest that TTFields may be the key to unlocking the value of immunotherapy in treating glioblastoma.”

TTFields are often combined with chemotherapy in cancer treatment. However, even with aggressive treatment, the prognosis for glioblastoma remains poor. Immunotherapy, while successful in many other cancer types, has also not proved effective for glioblastoma when used on its own.

However, in this study, adding immunotherapy to TTFields and chemotherapy was associated with a 70% increase in overall survival. Notably, patients with larger, unresected (not surgically removed) tumors showed an even stronger immune response to TTFields and lived even longer. This suggests that, when it comes to kick-starting the body’s immune response against the cancer, having a larger tumor may provide more targets for the therapy to work against.

Using Alternating Electric Fields to Unlock Immunotherapy

Pembrolizumab, the immunotherapy used in this study, is an immune checkpoint inhibitor (ICI), which enhances the body’s natural ability to fight cancers by improving T cells’ ability to identify and attack cancer cells.

However, there are typically few T cells in and around glioblastomas because these tumors originate in the brain and are shielded from the body’s natural immune response by the blood-brain barrier. This barrier safeguards the brain by tightly regulating which cells and substances enter from the bloodstream. Sometimes, this barrier even blocks T cells and other therapies that could help kill brain tumors.

This immunosuppressive environment inside and around the glioblastoma is what makes common cancer therapies like pembrolizumab and chemotherapy significantly less effective in treating it. Tran theorized the best way to get around this issue was to start an immune reaction directly inside the tumor itself, an approach known as in situ immunization, using TTFields.

This study demonstrates that combining TTFields with immunotherapy triggers a potent immune response within the tumor — one that ICIs can then amplify to bolster the body’s own defense against cancer.

“Think of it like a team sport — immunotherapy sends players in to attack the tumor (the offense), while TTFields weaken the tumor’s ability to fight back (the defense). And just like in team sports, the best defense is a good offense,” said Tran, who is also a member of the USC Norris Comprehensive Cancer Center.

The study analyzed data from 2-THE-TOP, a Phase 2 clinical 

, which enrolled 31 newly diagnosed glioblastoma patients who had completed chemoradiation therapy. Of those, 26 received TTFields combined with both chemotherapy and immunotherapy. Seven of these 26 patients had inoperable tumors due to their locations — an especially high-risk subgroup with the worst prognosis and few treatment options.

Patients in the trial were given six to 12 monthly treatments of chemotherapy alongside TTFields for up to 24 months. The number and duration of treatments were determined by patients’ response to treatment. The immunotherapy was given every three weeks, starting with the second dose of chemotherapy, for up to 24 months.

Patients who used the device alongside chemotherapy and immunotherapy lived approximately 10 months longer than patients who had used the device with chemotherapy alone in the past. Moreover, those with large, inoperable tumors lived approximately 13 months longer and showed much stronger immune activation compared to patients who underwent surgical removal of their tumors.

“Further studies are needed to determine the optimal role of surgery in this setting, but these findings may offer hope, particularly for glioblastoma patients who do not have surgery as an option,” said Tran.

Keck Medicine is participating in the multicenter Phase 3 clinical 

 to validate the efficacy of TTFields with immunotherapy and chemotherapy. Tran, who has been researching TTFields for more than a decade, serves as the chair of the steering committee for this trial. 

, neuro-oncologist with USC Norris, is the principal investigator of the Keck Medicine study site.

This Phase 3 trial, currently open at 28 sites across the United States, Europe and Israel, aims to enroll over 740 patients through April 2029, including those with gross total resection, partial resection or biopsy-only tumors to assess the extent of how surgically removing tumors influences immune response.

A recent study by Keck Medicine of USC suggests a promising combination therapy for glioblastoma, a challenging brain tumor with limited treatment options. The study indicates that Tumor Treating Fields (TTFields) therapy, when combined with immunotherapy (pembrolizumab) and chemotherapy (temozolomide), may significantly extend patient survival. TTFields disrupt tumor growth and enhance immune response, making immunotherapy more effective. The study showed a 70% increase in overall survival, especially in patients with larger, unresected tumors. A Phase 3 trial is underway to further validate these findings.

Electric field device placed on the scalp, along with immunotherapy and chemotherapy may help patients with glioblastoma live longer, particularly those with large, inoperable tumors.

Could Electric Fields Supercharge Immune Attack on the Deadliest Form of Brain Cancer?

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Surgeons from Keck Medicine of USC and UCLA Health have performed the world’s first-in-human bladder transplant. The surgery was successfully completed at Ronald Reagan UCLA Medical Center on May 4, 2025, in a joint effort by Inderbir Gill, MD, founding executive director of USC Urology, and Nima Nassiri, MD, urologic transplant surgeon and director of the UCLA Vascularized Composite Bladder Allograft Transplant Program.

“This surgery is a historic moment in medicine and stands to impact how we manage carefully selected patients with highly symptomatic ‘terminal’ bladders that are no longer functioning,” said Gill, who is also Chair and Distinguished Professor of Urology and Shirley and Donald Skinner Chair in Urologic Cancer Surgery with the Keck School of Medicine of USC. “Transplantation is a lifesaving and life-enhancing treatment option for many conditions affecting major organs, and now the bladder can be added to the list.”

“This first attempt at bladder transplantation has been over four years in the making,” Nassiri said. “For the appropriately selected patient, it is exciting to be able to offer a new potential option.”

Nassiri, formerly a urology resident with the Keck School and now assistant professor of urology and kidney transplantation at UCLA, and Gill worked together for several years at the Keck School to develop the new surgical technique, design a clinical trial and secure the necessary regulatory approvals.

Numerous pre-clinical procedures were performed both at Keck Medical Center of USC and OneLegacy, Southern California’s organ procurement organization, to prepare for this first-in-human bladder transplant.

The patient had been dialysis-dependent for seven years. He lost the majority of his bladder during surgery to resect cancer over five years ago, leaving the remainder of his bladder too small and compromised to function appropriately. Both of his kidneys were subsequently removed due to renal cancer.

To address these deficits, Drs. Gill and Nassiri performed a combined kidney and bladder transplant, allowing the patient to immediately stop dialysis and produce urine for the first time in seven years. First the kidney, then the bladder, were transplanted. The new kidney was then connected to the new bladder. The entire procedure took approximately eight hours.

“The kidney immediately made a large volume of urine, and the patient’s kidney function improved immediately,” Nassiri added. “There was no need for any dialysis after surgery, and the urine drained properly into the new bladder.”

“Despite the complexity of the case, everything went according to plan and the surgery was successful,” said Gill. “The patient is doing well, and we are satisfied with his clinical progress to date.”

The recovery of the kidney and bladder from the donor was performed at OneLegacy’s Transplant Recovery Center in Azusa, Calif. All parts of the procedure, including surgery and post-surgical monitoring during the transplantation, were aligned with the highest current clinical and research standards.

How a bladder transplant may benefit patients

Millions of people around the globe experience some degree of bladder disease and dysfunction. Some develop terminal bladders that are either non-functioning and/or cause constant pain, repeated infections and other complications. Current treatment for severe terminal cases of bladder dysfunction or a bladder that has been removed due to various conditions includes replacement or augmentation of the urinary reservoir. These surgeries use a portion of a patient’s intestine to create a new bladder or a pathway for the urine to exit the body.

“While these surgeries can be effective, they come with many short-and long-term risks that compromise a patient’s health such as recurrent infections, compromised kidney function and digestive issues,” said Gill.

“A bladder transplant, on the other hand, delivers a more ‘normal’ urinary reservoir and may circumvent some of the challenges associated with using the intestine,” said Nassiri.

The biggest risks of organ transplant are the body’s potential rejection of the organ and side-effects caused by the mandatory immunosuppressive drugs given to prevent organ rejection.

“Because of the need for long-term immunosuppression, the best current candidates are those with a pre-existing organ transplant or those who need a combined kidney and bladder transplant,” said Nassiri.

As a first-in-human attempt, there are naturally many unknowns associated with the procedure, such as how well the transplanted bladder will function immediately and over time, and how much immunosuppression will ultimately be needed.

“Despite the unknowns, our goal is to understand if bladder transplantation can help patients with severely compromised bladders lead healthier lives,” said Gill.

Collaborative research and development leading to the transplant

Bladder transplants have not been done previously, in part because of the complicated vascular structure of the pelvic area and the technical complexity of the procedure. As part of the research and development stage, Gill and Nassiri successfully completed numerous practice transplantation surgeries at Keck Medical Center of USC, including the first-ever robotic bladder retrievals and successful robotic transplantations in five recently deceased donors with cardiac function maintained on ventilator support. 

Several non-robotic trial runs of bladder recovery were performed at OneLegacy by Gill and Nassiri, allowing them to perfect the technique while working alongside multidisciplinary surgical teams.

The bladder transplant was done as part of a UCLA clinical trial. Gill and Nassiri hope to perform more bladder transplants together in the near future.

Under Gill’s leadership, USC Urology has rapidly established itself as a pioneer and world leader in the most advanced robotic urologic oncologic surgeries for kidney, bladder, prostate, testicular and penile cancers, and has achieved important milestones leveraging machine learning and artificial intelligence to optimize patient outcomes.

USC Norris Comprehensive Cancer Center has launched a cutting-edge radiation oncology and imaging center in Newport Beach, featuring advanced technology like the RefleXion X1 system for SCINTIX biology-guided radiation therapy (BgRT). This innovative approach uses PET radiotracers to track and treat cancer cells in real-time, minimizing damage to healthy tissue. The center enhances cancer care accessibility in Orange County, offering multidisciplinary services in collaboration with Advanced Radiotherapy Technologies. USC Norris continues to expand its presence, providing world-class, personalized cancer treatment options to the community.

Historic surgery, the result of years of research at Keck Medicine of USC and UCLA Health, opens the door for improved treatment of non-functioning bladders

USC, UCLA Team Up for the World’s First-in-Human Bladder Transplant

Keck Medicine of USC – Newport Beach Radiation Oncology and Imaging

, a state-of-the-art radiation oncology and imaging center, at 4590 MacArthur Blvd. in Newport Beach.

The 12,500 square-foot clinical space houses new-to-market imaging and radiation therapy technology in a serene, beach-inspired space designed to help patients feel at ease.

“Our new radiation oncology and imaging center demonstrates our ongoing commitment to providing Orange County with world-class care,” said 

, chief executive officer of Keck Medicine. “We recognize the importance of keeping cancer care close to home and are proud to expand our presence in the community.”

The center is equipped with PET-CT imaging and CT scanners for diagnosis, treatment simulation and monitoring, as well as two state-of the-art linear accelerators to deliver precision radiation therapy treatment.

Keck Medicine of USC – Newport Beach Radiation Oncology and Imaging will be the first clinical site in Orange County, and just the third in California, to offer 

 biology-guided radiation therapy (BgRT) using the new-to-market RefleXion X1 system. 

Unlike other types of radiation therapy that use static images of a patient’s anatomy to map treatment areas, BgRT is the first and only radiation therapy delivery modality that uses a PET radiotracer compound that, once injected into the body, interacts with cancer cells to send up-to-the-minute “signals” about the location of cancer cells, even as the patient breathes or moves slightly. This helps radiation oncologists track, target and treat cancer cells in real time while minimizing damage to healthy cells, which may alleviate some of the side effects of radiation.

BgRT also eliminates the need for placing markers (tiny metal objects positioned inside the patient in or near cancerous tissue to identify where to deliver treatment), as well as enables radiation oncologists to more efficiently treat multiple tumor locations in the same course of therapy.

BgRT recently received breakthrough device designation from the U.S. Food and Drug Administration for treating lung tumors and is currently approved for certain patients with lung and bone tumors.

Keck Medicine will install a second X1 system with BgRT at a medical facility in Pasadena opening later this year. It will be the first university-based academic institution to offer BgRT at multiple locations, bringing new cancer treatment options for the Los Angeles area, Orange County and surrounding communities.

“This groundbreaking technology enables us to provide the best possible care and offer treatment for patients whose options may be very limited,” said 

, radiation oncologist and director of clinical operations, regional radiation oncology clinics, with Keck Medicine. Tao is also clinical associate professor of radiation oncology with the 

. “We are thrilled to be the first to offer this revolutionary and potentially life-saving treatment to patients in Orange County.”

Keck Medicine of USC – Newport Beach Radiation Oncology and Imaging is less than 15 minutes away from USC Norris’ oncology locations in Newport Beach and Irvine, where patients can make appointments with respected medical oncologists who have served Orange County for decades, and who treat more medical oncology outpatients in Newport Beach than any other provider.

“This new location expands our spectrum of cancer services in Orange County, ranging from diagnostic imaging to multiple treatment options that optimize outcomes and provide personalized radiation medicine,” said 

, radiation oncologist with Keck Medicine and chair and professor of radiation oncology with the Keck School.

As one of the eight original National Cancer Institute-designated Comprehensive Cancer Centers in the United States, 

 has revolutionized cancer treatment, research and prevention for 50 years. In 2024-25, U.S. News & World Report ranked USC Norris Comprehensive Cancer Center among the top 25 cancer centers nationally and recognized 

“The addition of this new location means so much for our patients and their loved ones,” said 

, medical oncologist with USC Norris Comprehensive Cancer Center, practicing in Newport Beach. “Our convenient location near our medical oncology offices means that our patients can truly benefit from multidisciplinary, collaborative care from doctors they know and trust.”

To make an appointment at Keck Medicine of USC – Newport Beach Radiation Oncology and Imaging, call (949) 507-6700 or visit 

USC Norris opened the new facility in collaboration with Advanced Radiotherapy Technologies (ART Health), a leading developer of radiotherapy centers. ART Health is a division of Kingsbarn Realty Capital, a national investment manager.

USC Norris Comprehensive Cancer Center has opened Keck Medicine of USC – Newport Beach Radiation Oncology and Imaging, a radiation oncology center.

USC Norris Comprehensive Cancer Center Opens State-of-the-Art Newport Beach Radiation Oncology and Imaging Center

The California Institute for Regenerative Medicine has awarded a $6 million grant to USC investigators pioneering a new first-of-its-kind genetic therapy for glioblastoma, a severe form of brain cancer. The treatment would be the first gene therapy for glioblastoma to use a novel, more precise delivery system that is less likely to harm non-cancerous cells.

Glioblastoma is an aggressive and fast-growing cancer originating in the brain that occurs primarily in adults and has no known cure. Patients diagnosed with this type of tumor have a five-year survival rate of just 5 percent. The cancer’s location—in the sensitive brain—combined with its heterogeneity make treatment notoriously difficult. Tumor composition varies widely across patients and even within individual tumors as abnormal cells continuously mutate.

“The personalized treatment you hear about for this type of cancer often feels like a game of whack-a-mole,” said principal investigator 

, USC associate professor of neurological surgery and neurology, division chief of neuro-oncology at the 

. “By the time you’ve sequenced a patient’s tumor, identified all its mutations, personalized a treatment plan, and developed the therapy, the tumor you’re treating is no longer the same tumor. There’s a new set of mutations. So, you wind up chasing your tail.”

The three-year grant, led by USC in collaboration with members of the Zolotukhin Lab at the University of Florida, builds on three advances the team has made towards a novel GBM treatment, with the goal of moving it closer to clinical trials.

Tran’s team developed a new AI technology to analyze large genetic data sets and identify “master regulators” within glioblastoma—key genes that define a brain tumor and are essential for its survival. Of the nine master genes they found, seven were developmental, or typically active only in early fetal development, where they support rapid growth before becoming dormant.

“Tumor cells are smart,” Tran said, who is also a member of the Tumor Immunology and Microenvironment Program at the 

. “They go back and pull these developmental genes out from dormancy and use them to fuel their own uncontrollable growth.” Tests in his lab showed that targeting these developmental genes with anti-cancer therapy led to tumor collapse. “You only need to deplete a few of these master genes,” Tran said. “Once they’re gone, the cancer doesn’t stand a chance.”

In addition to identifying new targets, researchers have discovered a promising vehicle for delivering therapy to the cancer using a common virus known as AAV (adeno-associated virus). While viruses serve as vital tools in many gene therapies, when it comes to glioblastoma they typically lack precision, infecting not just the diseased cells but also surrounding healthy brain cells.

“Too often, these viruses have a carpet-bombing effect,” Tran said. “That’s not ideal for brain cancers.”

The USC team created a library of approximately 10 billion different variants of these AAV viruses and exhaustively screened them, looking for any viruses capable of infecting glioblastoma cells without infecting normal brain tissue. One candidate, a virus known as T6, fit the bill: in mice carrying human glioblastoma tumors, this potent virus demonstrated a high preference for infecting cancer cells and little else. When used to deliver a targeting drug already identified by Tran’s team, the virus showed cure rates approaching 70 to 90 percent in these mouse models. “That’s almost unheard of,” Tran said. CIRM funding will enable the team to prepare this new delivery vehicle and drug target for clinical trials.

Patients with aggressive brain tumors typically undergo a procedure called conduction-enhanced delivery (CED), where a surgeon implants a catheter into the tumor to deliver the gene therapy and cellular treatment. This clinical process is ripe for improvement.

“Historically, CED has been done somewhat blindly,” Tran said. “After initial imaging to identify the tumor’s coordinates, the surgeon inserts the catheter into the middle of the tumor and hopes that it will be effectively delivered to the entire tumor. But tumors are more complicated than that.”

If the catheter hits a “blind pouch” in the tumor, the medication remains stuck there and can’t flow outward. To tackle the problem, USC investigators and collaborators have started engineering a new computational method to map the tumors’ flow patterns, which function like riverbeds. This mapping will provide surgeons with enhanced guidance for optimal catheter placement and maximum drug diffusion. The CIRM grant will support further improvements to the technology, which Tran hopes will make its way into clinical settings. “The goal is to safely deliver the highest concentration of effective therapy to the patient,” he said.

The grant team, which includes USC neuropathologists, computational biologists, and neurosurgeons, will collaborate with the USC/CHLA cGMP facility. Designed to manufacture cell and gene therapies under the Food and Drug Administration’s current good manufacturing practice (cGMP) standards, the facility will ensure that all treatment products and protocols meet human safety and efficacy standards. The researchers also plan more preclinical testing to reconfirm the results achieved in laboratory models.

For Tran, it’s a profoundly hopeful moment. “This is the best time to be in this field as a researcher and as a clinician,” he said. “When I started seventeen years ago, I spent most of my time telling patients to get their affairs in order. Today, we’re talking about prolonging survival. In the next five to ten years, we’re going to see major changes in what a diagnosis of glioblastoma means for patients.”

USC researchers have received a $6 million grant to develop a pioneering genetic therapy for glioblastoma, a highly aggressive brain cancer. This therapy utilizes a novel delivery system that targets cancer cells while sparing healthy ones. The team has identified key "master regulator" genes essential for tumor survival and developed a virus-based delivery vehicle with high specificity for cancer cells. Additionally, they are enhancing tumor mapping techniques to improve drug delivery. The grant supports further development and preclinical testing, aiming to advance the therapy towards clinical trials.

The California Institute for Regenerative Medicine has awarded a $6 million grant to USC investigators pioneering a new genetic therapy to treat glioblastoma.

New Grant Funds First-of-Its-Kind Gene Therapy to Treat Aggressive Brain Cancer

A new study from the USC Norris Comprehensive Cancer Center has found evidence that targeting CD47, a protein that is part of the innate immune system, could be a key step in fighting colorectal cancer.

It is one of the first indications that targeting part of the innate immune system, combined with traditional immunotherapy drugs which work on the adaptive immune system, could be more effective in fighting colorectal cancer. The findings were just published in the Journal for ImmunoTherapy of Cancer.

Traditional immunotherapies, known as immune checkpoint inhibitors, have transformed cancer care by helping the body’s immune system fight cancer like it does other diseases. They do this by blocking immune checkpoints – proteins that act like brakes for the immune system to keep it from attacking healthy cells. Cancer cells exploit these proteins to evade detection by immune cells, but immune checkpoint inhibitors prevent that.

Until recently, immunotherapies only targeted the body’s learned immune response, once cancer cells had already slipped by the body’s first line of defense against disease, known as the innate immune system.

“Up until now, immune checkpoint inhibitors targeting the adaptive immune system have been the mainstream in immunotherapy,” said first author Hiroyuki Arai, MD, PhD, a former postdoctoral researcher at the cancer center, part of the Keck School of Medicine of USC. “But in our current study, we focused on CD47, a checkpoint molecule in the innate immune system.”

The researchers knew colorectal cancer cells use the immune checkpoint CD47 to dodge macrophages, innate immune cells that would otherwise target and destroy them. But how exactly do cancer cells manipulate CD47, and what could this mean when it comes to treating colon cancer?

In the present study, funded in part by the National Institutes of Health, researchers analyzed DNA and RNA from 14,287 colorectal cancer tumors to answer those questions. They compared tumors with higher levels of CD47 expression to those with lower levels, finding that higher levels were linked to more aggressive tumors, more activated cancer pathways and more immune cells inside the tumor.

Those findings suggest that developing an immune checkpoint inhibitor drug that can block the activity of CD47 could improve outcomes for colon cancer patients, many of whom are not well served by existing immunotherapy drugs.

“The most important takeaway is this data suggests that CD47 is a very attractive target for drug development,” said senior author Heinz-Josef Lenz, MD, deputy director for research programs and co-director for the Rosalie and Harold Rae Brown Center for Cancer Drug Development at the USC Norris cancer center.

To delve into the details of CD47’s role in colon cancer, researchers sequenced the DNA and RNA from 14,287 colorectal tumor samples stored within the Caris Life Sciences database. The researchers divided cases into two groups: those with high CD47 expression (above the median level) and those with low CD47 expression (below the median level). They then compared the two groups, looking for differences in immune signaling and other biological processes.

Higher expression of CD47 within a tumor was associated with higher oncogenic signaling, which means that tumors are growing and may be spreading. Higher CD47 expression was also linked to changes in several key immune pathways, including suppressing the signal used to activate macrophages, which would otherwise eliminate the cancer cells.

The researchers also found that higher levels of CD47 were associated with the formation of new blood vessels, a process called angiogenesis. In cancer research, angiogenesis is a red flag because it is typically a sign that tumors are growing larger.

Taken together, these findings point to CD47 as a top target for new colorectal cancer drugs. It could be used alongside one of more of the currently available therapies, including chemotherapy, angiogenesis inhibitors and adaptive immune checkpoint inhibitors, said Arai, who is now an assistant professor of clinical oncology at the St. Marianna University School of Medicine in Kawasaki, Japan.

“The key is to develop an antibody or an engineered immune cell that can inhibit CD47 signaling, but it has to be used in combination with other drugs. The right combination is not clear yet, so more research is needed,” said Lenz, who is also a professor of medicine and preventive medicine at the Keck School of Medicine.

Lenz, Arai and their team are also studying other methods of shrinking colorectal cancer tumors, including with compounds that stimulate macrophages to attack cancer cells.

In addition to Lenz and Arai, the study’s other authors are Francesca Battaglin, Jingyuan Wang, Sandra Algaze, Priya Jayachandran, Shivani Soni, Wu Zhang, Yan Yang, Joshua Millstein and Jae Ho Lo from the Norris Comprehensive Cancer Center, Keck School of Medicine of USC, University of Southern California; Nishant Gandhi, Joanne Xiu and Micharl W. Korn from Caris Life Sciences Inc.; Davendra Sohal from University of Cincinnati Medicine; Richard Goldberg from the West Virginia University Cancer Institute; Michael J. Hall from Fox Chase Cancer Center, Philadelphia, Pennsylvania; Aaron James Scott from the University of Arizona Cancer Center, Department of Medicine; Jimmy J. Hwang from GI Medical Oncology Levine Cancer Institute; Emil Lou from the University of Minnesota; Benjamin Weinberg from Georgetown University Medical Center; John Marshall from Georgetown University; and Sanjay Goel from Rutgers Cancer Institute of New Jersey.

This work was supported by the National Cancer Institute of the National Institutes of Health [P30CA014089]; the Gloria Borges WunderGlo Foundation; the Dhont Family Foundation; the Victoria and Philip Wilson Research Fund; the San Pedro Peninsula Cancer Guild; Ming Hsieh Research and the Daniel Butler Research Fund.

Targeting CD47, a protein in the innate immune system, may enhance colorectal cancer treatment when combined with traditional immunotherapies. CD47 allows cancer cells to evade macrophages, leading to more aggressive tumors. Researchers analyzed 14,287 colorectal cancer tumors, finding higher CD47 expression linked to increased oncogenic signaling and angiogenesis. Developing drugs targeting CD47 could improve patient outcomes, especially when used with existing therapies. Further research is needed to determine the optimal combination of treatments to inhibit CD47 signaling effectively.

Researchers find evidence that simultaneously targeting the innate and adaptive immune systems holds promise for treating aggressive colon cancer cases.

USC Study Explores New Insights into Innate Eesistance for Immunotherapies in Colorectal Cancer

USC Norris Comprehensive Cancer Center, part of Keck Medicine of USC, will open a Newport Beach location offering the latest advancements in radiation therapy and diagnostic imaging. The treatment center, which will open in early 2025, will feature cutting-edge cancer technologies that are yet to be available in Orange County, providing new therapeutic options and optimizing patient outcomes.

The new location address is 4590 MacArthur Blvd. in Newport Beach, less than 15 minutes away from USC Norris’ oncology centers in Newport Beach and Irvine. Those centers are staffed by respected oncologists who have served Orange County for decades, and who treat more medical oncology outpatients in Newport Beach than any other providers.

“We are excited to build upon USC Norris’ well-established, robust cancer practices in Orange County and broaden our spectrum of services,” said Louis Vandermolen, MD, medical oncologist with USC Norris Oncology/Hematology. “Our radiation oncology and imaging center is a testament to our continued commitment to offer world class, comprehensive cancer services for patients without having to leave the local community.”

As one of the eight original National Cancer Institute-designated Comprehensive Cancer Centers in the United States, USC Norris has revolutionized cancer treatment, research and prevention for 50 years. In 2024-25, U.S. News & World Report ranked USC Norris Comprehensive Cancer Center among the top 25 cancer centers nationally and recognized USC Norris Cancer Hospital as a Best Specialty Hospital.

USC Norris is collaborating on their new Newport Beach facility with Advanced Radiotherapy Technologies (ART Health), a leading developer of radiotherapy centers. ART Health is a division of Kingsbarn Realty Capital, a national investment manager.

The new USC Norris location will feature new-to-market technology not yet available in Orange County 

USC Norris Comprehensive Cancer Center to Open Radiation Oncology and Imaging Center in Newport Beach

For adults with acute lymphoblastic leukemia (ALL), a type of cancer that originates in the bone marrow, allogeneic stem cell transplantation (more commonly known as a bone marrow transplant) may be necessary for survival. But for Hispanic patients, finding an identically matched donor within their family or through the bone marrow donor registry can be challenging, with only a 30% chance of finding a matching relative and a 48% chance of identifying a matching bone marrow donor through the national donor registry.

 suggests that a bone marrow transplant from a haploidentical, or half-identical relative, may greatly increase patients’ odds of success, in addition to being easier to find. Parents and children are guaranteed half-matches, while siblings have a 50% chance of being half-matches, which is twice as likely as finding a fully matched sibling (25%).

The study retrospectively assessed outcomes from 88 patients with B-cell ALL (an aggressive type of leukemia wherein the body overproduces abnormal white blood cells called B-lymphocytes) who underwent a bone marrow transplant at 

, part of Keck Medicine. Bone marrow donors included fully matched sibling donors, fully matched unrelated donors identified through the national donor registry, and half-matched donors from the patient’s family. The study assessed patient outcomes after two years following transplantation.

Patients who received their transplant from a half-identical relative were about 70% more likely to avoid relapse than those who received a bone marrow transplant from a fully identical relative.

Compared to patients who received a bone marrow transplant from an identically matched registered donor, half-identical relative transplant recipients were more than twice as likely to avoid both relapse and graft versus host disease, a debilitating condition wherein the body rejects the transplanted stem cells.

“These results suggest that Hispanic patients may benefit more from receiving a bone marrow transplant from a half-matched parent, child or sibling, rather than a full match from the national donor registry,” said 

 and lead author on the study. “This creates opportunities for patients to receive a life-saving procedure that may otherwise be out of reach.”

Prior to receiving a bone marrow transplant, potential recipients must first find a donor with a matching human leukocyte antigen (HLA) tissue type. HLAs are proteins on cells that act like a signature or passcode for the immune system. When white blood cells find foreign cells with an unfamiliar HLA type, it triggers an attack response. To ensure that a patient’s immune system accepts the new bone marrow stem cells, doctors aim to find a donor with the closest possible match for the patient.

Because HLA tissue type is inherited, patients often look first to immediate family members as potential donors. Unrelated matched donors may be available through the 

, which manages the largest registry of potential bone marrow donors.

Despite the size of the NMDP registry, certain ethnic backgrounds have more difficulties finding a match due to being underrepresented in the registry. While white patients have a 79% chance of finding a match through the registry, Hispanic patients are only 48% likely to find a match.

Hispanic patients have a higher incidence of ALL compared to white patients, and often present with higher-risk disease characteristics that are associated with more challenging outcomes and require complex care. This makes finding a bone marrow donor all the more crucial.

New Opportunities with Half-Identical Donors

Bone marrow transplants from half-identical family members have been performed more frequently due to the challenges in finding a fully matched donor, as well as due to treatment advances that help the body accept the new cells despite not having a fully matched HLA type.

Yaghmour hopes the study results will inspire larger clinical trials to further investigate the findings and provide insight as to why bone marrow transplants from half-identical relatives result in positive outcomes, particularly among patients with high-risk subtypes of ALL.

“These findings are a strong basis to continue researching the clinical benefits of haploidentical bone marrow donation, particularly among patient groups with historically limited access to fully matched donors,” said Yaghmour, who is also the associate director of transplant and cellular therapy with USC Norris and an associate professor of clinical medicine at the 

. “Future studies can potentially address health disparities while optimizing outcomes, and ultimately provide more hope for all patients facing this difficult diagnosis.”

A new study from Keck Medicine of USC suggests that bone marrow transplants from haploidentical (half-identical) relatives significantly improve outcomes for Hispanic patients with acute lymphoblastic leukemia (ALL). This approach is particularly beneficial given the challenges Hispanic patients face in finding fully matched donors. The study found that patients receiving transplants from half-identical relatives had a higher likelihood of avoiding relapse and graft versus host disease compared to those receiving transplants from fully matched donors. These findings could lead to more accessible and effective treatment options for this patient population.

A new study may open life-saving opportunities for Hispanic patients, who are one-third less likely to find a fully matched donor from the national registry than white patients.

USC Norris Comprehensive Cancer Center