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.

Articles

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

Articles

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

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

Half-Matched Family Donors Offer Best Outcomes for Hispanic Patients Undergoing Bone Marrow Transplants