Clinical features and multiplatform molecular analysis assist in understanding patient response to anti‐pd‐1/pd‐l1 in renal cell carcinoma

Abstract

Predicting response to ICI therapy among patients with renal cell carcinoma (RCC) has been uniquely challenging. We analyzed patient characteristics and clinical correlates from a retro-spective single‐site cohort of advanced RCC patients receiving anti‐PD‐1/PD‐L1 monotherapy (N = 97), as well as molecular parameters in a subset of patients, including multiplexed immunofluores-cence (mIF), whole exome sequencing (WES), T cell receptor (TCR) sequencing, and RNA sequencing (RNA‐seq). Clinical factors such as the development of immune‐related adverse events (odds ratio (OR) = 2.50, 95% confidence interval (CI) = 1.05–5.91) and immunological prognostic parame-ters, including a higher percentage of circulating lymphocytes (23.4% vs. 17.4%, p = 0.0015) and a lower percentage of circulating neutrophils (61.8% vs. 68.5%, p = 0.0045), correlated with response. Previously identified gene expression signatures representing pathways of angiogenesis, myeloid inflammation, T effector presence, and clear cell signatures also correlated with response. High PD‐ L1 expression (>10% cells) as well as low TCR diversity (≤644 clonotypes) were associated with improved progression‐free survival (PFS). We corroborate previously published findings and provide preliminary evidence of T cell clonality impacting the outcome of RCC patients. To further bi-omarker development in RCC, future studies will benefit from integrated analysis of multiple molecular platforms and prospective validation.