Many patients with metastatic renal cell carcinoma are treated with immune checkpoint inhibitors as part of their systemic regimens, but only a small subset of patients achieve durable long-term or curative responses. To identify molecular biomarkers for these exceptional responders and better predict which patients benefit most, researchers led by Sachet Shukla, Ph.D., utilized whole-exome and RNA sequencing to analyze pre-treatment tumor samples and matched germline samples from treated patients in two clinical trials.
The researchers identified several potential drivers of exceptional responses, including high clonal neoantigen load, heightened metabolic activity, and humoral immunity – a type of immune response using antibodies as evidenced by the presence of tertiary lymphoid structures. Prospective validation is needed before these biomarkers become clinically viable, but this multi-institutional study lays the foundation for better understanding the mechanisms underlying responses in this important subset of patients.