A recent study published in Nature Cancer has identified key factors contributing to exceptional responses in patients with metastatic clear cell renal cell carcinoma (mccRCC) undergoing immunotherapy. Researchers from Yale Cancer Center, in collaboration with Dana-Farber Cancer Institute and The University of Texas MD Anderson Cancer Center, analyzed data from over 1,000 mccRCC patients worldwide who received standard immunotherapy treatments. The study focused on two treatment combinations: PD-1/PD-L1 inhibitors with CTLA-4 inhibitors (IO/IO) and PD-1/PD-L1 inhibitors with VEGF-receptor inhibitors (IO/VEGF). Findings revealed that patients exhibiting exceptional responses to the IO/IO combination had a significantly higher number of clonal neoantigens—unique DNA mutations present across all cancer cells, making them identifiable targets for the immune system. Conversely, exceptional responders to the IO/VEGF combination displayed robust B-cell receptor signaling pathways, the presence of tertiary lymphoid structures (immune cell aggregates that facilitate anti-tumor activity), and increased metabolic activity within the tumor microenvironment.
These insights suggest that multiple biological pathways can lead to outstanding responses in mccRCC patients undergoing immunotherapy. Understanding these distinct mechanisms may aid in tailoring treatment strategies to individual patients, potentially enhancing the efficacy of immunotherapeutic approaches in kidney cancer. As co-senior author Dr. David Braun noted, “It’s very complex, and there are many factors that contribute to a strong response to treatment. We hope by uncovering these factors, it can improve patient response and treatment options.” Click for More Details
