Immune checkpoint blockade in renal cell carcinoma

Published on March 31, 2016   58 min

Other Talks in the Series: Immunotherapy of Cancer

Other Talks in the Series: The Kidney in Health and Disease

Hello, my name is David McDermott. And I'm a medical oncologist at Beth Israel Deaconess Medical Center in Boston, Massachusetts. And I'm leader of the kidney cancer program at the Dana Farber Harvard Cancer Center as well as an associate professor of medicine at Harvard Medical School. And I'm here to talk to you today about immune checkpoint blockade in renal cell carcinoma.
During my career as a medical oncologist, there have been two waves of interest in immune therapy for solid tumors. I became a physician during the first wave. I graduated from medical school in 1992, when the use of cytokine-based immunotherapy was just reaching its peak, with the approval, in the United States, of high dose interleukin 2. Right after graduating from medical school, I began to focus on medical oncology. I was interested in learning more about the immune response to cancer and began doing research in this area. Needless to say, over the next 10 or 15 years, the interest in solid tumor immunotherapy began to decline dramatically, maybe sort of coinciding with my career in medical research. There was a significant rise in the application of molecularly targeted therapies, which began to replace these agents, particularly in kidney cancer, where many of the VEGF targeted agents proved superior to the old cytokine-based immunotherapies. However, in the last five to six years, there's been a dramatic increase in interest in the field of immunotherapy not just for kidney cancer but for other solid tumors. And these forms of immunotherapy have included vaccines, recombinant t-cell receptors, bi-specific T-cell engagers, but, most interestingly, these so-called checkpoint inhibitors, which have recently become approved in metastatic kidney cancer.
Why is this renewed interest possible? Well, we have a much better sense of how the immune system controls cancer or, more importantly, how tumors use complex and sometimes overlapping mechanisms to suppress the immune response to cancer. They do this by many ways. On this slide, we see that tumors can inhibit tumor antigen presentation, through the down regulation of MHC class I. They can suppress immunosuppressive factors in the tumor microenvironment, like TGF-beta. They can also recruit immunosuppressive cell types into the microenvironment, for example, T-regulatory cells, producing immunosuppression, locally. But probably most importantly, they can express these so-called checkpoint inhibitors, which work to inhibit immune cells that have actually detected the tumor, found their way into the tumor microenvironment, and would otherwise kill the tumor if it wasn't for their expression, on the tumor or on immune cells near the tumor. These checkpoint inhibitors sort of act like barbed wire, deleting T-cells that have found their way all the way to the tumor but are prevented from killing it.

Immune checkpoint blockade in renal cell carcinoma

Embed in course/own notes