Opinion
Video
Author(s):
“To add to the complexity, is the issue of intratumoral heterogeneity, where some clones may develop these resistance mechanisms and lose response over time or become resistant, while other clones will continue to respond,” says Kate H. Gessner, MD, PhD.
In this video, Kate H. Gessner, MD, PhD, discusses the mechanisms of immunotherapy failure in renal cell carcinoma, which was discussed during a case-based session at the 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium in San Francisco, California. Gessner is an associate professor of urology at the University of North Carolina School of Medicine in Chapel Hill.
Video Transcript:
There's a lot of work investigating these mechanisms currently. There's a wide variety of mechanisms of immunotherapy failure. Dr. Matt Campbell today will go into detail on each of these, but in general, there's primary resistance, adaptive resistance, and acquired resistance. Primary resistance is when the tumor doesn't respond to immunotherapy. Adaptive resistance is when the cancer cells can be recognized by the immune system, but then they adapt to protect themselves and evade the immune response. Then acquired resistance is when the tumor responds initially, but after a period of time, it relapses and progresses.
On a cellular level, there's a variety of mechanisms for each of those, which can be specific to the type of immunotherapy as well. And then additionally, to add to the complexity, is the issue of intratumoral heterogeneity, where some clones may develop these resistance mechanisms and lose response over time or become resistant, while other clones will continue to respond. This can make the decision on when to change therapy quite difficult if some lesions are responding and others aren't.
This transcript was AI generated and edited by human editors for clarity