Shiuan E, Reddy A, Dudzinski SO, Lim AR, Sugiura A, Hongo R, Young K, Liu XD, Smith CC, O'Neal J, Dahlman KB, McAlister R, Chen B, Ruma K, Roscoe N, Bender J, Ward J, Kim JY, Vaupel C, Bordeaux J, Ganesan S, Mayer TM, Riedlinger GM, Vincent BG, Davis NB, Haake SM, Rathmell JC, Jonasch E, Rini BI, Rathmell WK, Beckermann KE. Clinical Features and Multiplatform Molecular Analysis Assist in Understanding Patient Response to Anti-PD-1/PD-L1 in Renal Cell Carcinoma. Cancers. 2021 Mar 23;13(13). PMID: 33806963 [PubMed] PMCID: PMC8004696
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 retrospective 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 immunofluorescence (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 parameters, including a higher percentage of circulating lymphocytes (23.4% vs. 17.4%, = 0.0015) and a lower percentage of circulating neutrophils (61.8% vs. 68.5%, = 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 biomarker development in RCC, future studies will benefit from integrated analysis of multiple molecular platforms and prospective validation.