Stefani Spranger, PhD, postdoctoral fellow, Cancer Research Institute at The University of Chicago Medicine, discusses how the presence or absence of CD8-positive T cells can affect treatment approaches for patients with melanoma.

Spranger's research at The University of Chicago Medicine began with a focus on how to delineate patients with melanoma into those who have CD8-positive T cells present in the tumor microenvironment and those who lack those cells. She eventually discovered that some patients actually have both tumor phenotypes, ones with those T cells and ones without.

As she continued to study these differences in the tumor microenvironments, she and her colleagues identified the upregulation of the WNT/β-catenin pathway, which is a factor that actively excludes CD8-positive T cells from the tumor microenvironment. It does this by systemically blocking both the activation and recruitment of those T cells into the environment, Spranger explains. This can potentially act as an invasion mechanism for how tumors can evade a potent antitumor immune response induced by immunotherapy agents.

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Stefani Spranger, PhD, postdoctoral fellow, Cancer Research Institute at The University of Chicago Medicine, discusses how the presence or absence of CD8 T cells can affect treatment approaches for patients with melanoma.

Stefani Spranger on the Role of CD8 T Cells in Melanoma

Stefani Spranger, PhD, postdoctoral fellow, Cancer Research Institute at The University of Chicago Medicine, discusses immune checkpoint blockade therapies that are currently being used to treat patients with melanoma.

Checkpoint blockade therapies target immune inhibitory molecules on CD8-positive T cells, explains Spranger. By blocking those immune inhibitory pathways, the cells are essentially reactivated, and they regain their function to fight the cancer.

Spranger also sheds light on the need to identify predictive and precise biomarkers in melanoma. Currently, most research looks at PD-L1 expression as a biomarker for patients. PD-L1 is upregulated in response to T-cell activation molecules that are secreted by T cells, says Spranger. Thus, PD-L1 expression is an indicative marker of the presence of CD8-positive T cells on the tumor.

However, Spranger delves into some of the imperfections associated with this biomarker, as well. Some tumor cells have intrinsic methods to upregulate PD-L1, which would mean there is no presence of T cells, and this can lead to false positives. In the future, Spranger hopes to see genomic-based approaches to ensure the certainty of the presence of T cells within the tumor microenvironment.

Stefani Spranger, PhD, postdoctoral fellow, Cancer Research Institute at The University of Chicago, discusses immune checkpoint blockade therapies that are currently being used to treat patients with melanoma.

Stefani Spranger on Checkpoint Blockade Therapies in Melanoma

Stefani Spranger, PhD, postdoctoral fellow at the University of Chicago, discusses recent findings about why a subgroup of patients with melanoma do not have T cells within their tumor microenvironment.

At the 2016 Society for Melanoma Research (SMR) Congress, Spranger discussed her findings that upregulation of the WNT/beta-catenin pathway within the tumor cell mediates the exclusion of T cells from the microenvironment. This is because a subtype of dendritic cells (CD141-positive) must be present to recruit T cells back into the tumor.

Stefani Spranger, PhD, postdoctoral fellow at the University of Chicago, discusses recent findings about why a certain subgroup of patients with melanoma do not have T cells within their tumor microenvironment. 

Stefani Spranger Explores the Absence of T Cells in Melanoma Subtypes

Stefani Spranger, PhD, postdoctoral fellow, Cancer Research Institute at The University of Chicago, discusses the basic knowledge all oncologists should have regarding immunotherapy.

Immunotherapy actives the immune system to recognize and then destroy the cancer, says Spranger. The main players in this recognition are CD8-positive T cells. These are the T cells in viral infections that are responsible for killing the infected cells.

With cancer, because the body’s own cells are attacking it, the CD8-positive T cells do not know to fight it. Immunotherapy educates the immune system to do this and could possibility be used to fight most of the cancers that are currently out there, says Spanger.

​Stefani Spranger, PhD, postdoctoral fellow, Cancer Research Institute at The University of Chicago, discusses the basic knowledge all oncologists should have regarding immunotherapy.
 

Stefani Spranger on What Every Oncologist Should Know About Immunotherapy

Stefani Spranger, PhD, postdoctoral fellow, Cancer Research Institute at The University of Chicago, discusses the differences between immunotherapy and chemotherapy.

With chemotherapy, any proliferating cell is targeted and will die. Immuooncology takes a very different approach, says Spranger, because the immune system is for specific at recognizing what the malfunctioning cells are and only killing those cells.

 Another big difference is the immune system does have a memory and this memory plays out for the long-term, she says. If a drug is able to active the immune system to recognize that one particular cancer, the cancer will not be forgotten. When there is a recurrence, the immune system will still be able to recognize the same cancer and still be able to fight it.

Stefani Spranger, PhD, postdoctoral fellow, Cancer Research Institute at The University of Chicago, discusses the differences between immunotherapy and chemotherapy.
 

Stefani Spranger on Immunotherapy Versus Chemotherapy

Stefani Spranger, PhD, University Chicago Melanoma Intrinsic β-Catenin Committee, discusses the effect of melanoma intrinsic β-catenin signaling on immune exclusion and resistance to immunotherapies.

Melanoma intrinsic β-catenin, once its activated in melanoma, can mediate the exclusion of the immune system, says Spranger. Previous research has shown that t-cells can be used as predictive biomarker for the response rate of anti-PD-1 therapies.

When melanoma patients were segregated into those with a low t-cell gene signature and those with a high t-cell gene signature it was determined that the patients that did not have t-cells in their tumor microenvironment had β-catenin signaling, says Spranger.

Research on this topic is preliminary, says Sparnger, but once it is determined how the β-catenin pathway can be inhibited, it is possible to overcome resistance to immunotherapies.

Stefani Spranger, PhD, University Chicago Melanoma Intrinsic Î²-Catenin Committee, discusses the effect of melanoma intrinsic Î²-catenin signaling on immune exclusion and resistance to immunotherapies.

Stefani Spranger, PhD

Articles

Stefani Spranger on the Role of CD8 T Cells in Melanoma

Stefani Spranger on Checkpoint Blockade Therapies in Melanoma

Stefani Spranger Explores the Absence of T Cells in Melanoma Subtypes

Stefani Spranger on What Every Oncologist Should Know About Immunotherapy

Stefani Spranger on Immunotherapy Versus Chemotherapy

Stefani Spranger on Î²-Catenin Signaling and Overcoming Immunotherapy Resistance