CD40 expression correlates with response to immunotherapy in melanoma patients
By Wendy Bindeman
Ann Richmond, professor of pharmacology, and Chi Yan, a research assistant professor in the Richmond lab, recently published a study showing that expression of a protein called CD40 can be used to predict response to immunotherapy in malignant melanoma. Their work was published in November 2021 in the journal Molecular Cancer.
We sat down with Yan to learn more about this exciting new research.
What problem does your research address?
Immunotherapy, which harnesses the immune system to fight tumors, is a promising treatment strategy for many cancers, but it is not effective for all patients. It is still unclear why some people do not respond to these therapies. This paper examines the CD40 expression in normal and cancer tissues and the relationship between CD40 expression and response to immunotherapy. CD40 is part of a class of proteins called “co-stimulatory molecules” and is expressed on the surface of antigen-presenting cells (part of the immune system), a variety of non-blood cells, and some tumor cells. Activation of CD40 by binding of its ligand can stimulate anti-tumor immune responses.
A previous paper by our lab found that in melanoma, high CD40 expression correlated with anti-tumor immune responses, better prognosis, and positive responses to either immune checkpoint blockade therapy (which enhances the immune response) or targeted therapy. The current paper explores the role of CD40 in other cancer types using a bioinformatics approach.
What was unique about your approach to the research?
We used bioinformatic techniques to investigate the relationship between CD40 expression in tumors and corresponding normal tissues, as well as the response to immune checkpoint blockade therapy.
What were your findings?
We found that CD40 expression is positively correlated with an anti-tumor immune response and better patient survival. CD40 expression is also associated with a better response to immunotherapy in melanoma. In the pan-cancer analysis, we found that CD40 expression is frequently reduced in tumors (we found lowered expression levels in 11 cancer types), including in melanoma tumors that carry a mutation in a growth-promoting gene called RAS.
What are the benefits of this research?
Although immunotherapy has been revolutionary for metastatic melanoma, not all patients respond and there is a risk of serious side effects. We hope that CD40 expression will be examined as a potential marker for positive response to immune checkpoint blockade therapy for metastatic melanoma in order to better select patients who might benefit.
Where is this research taking you next?
We will be examining how CD40-activating antibodies might improve the response to immune checkpoint inhibitors for treatment of malignant melanoma. Promoting CD40-driven immune therapy in combination with targeted therapy in melanoma, could improve patient prognosis.
This research was funded by the Department of Veterans Affairs and the National Cancer Institute.
The article “Hiding in the dark: pan-cancer characterization of expression and clinical relevance of CD40 to immune checkpoint blockade therapy” was published in the journal Molecular Cancer in November 2021.