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

Eileen Shiuan, Anupama Reddy, Stephanie O. Dudzinski, Aaron R. Lim, Ayaka Sugiura, Rachel Hongo, Kirsten Young, Xian De Liu, Christof C. Smith, Jamye O’neal, Kimberly B. Dahlman, Renee McAlister, Beiru Chen, Kristen Ruma, Nathan Roscoe, Jehovana Bender, Joolz Ward, Ju Young Kim, Christine Vaupel, Jennifer BordeauxShridar Ganesan, Tina M. Mayer, Gregory M. Riedlinger, Benjamin G. Vincent, Nancy B. Davis, Scott M. Haake, Jeffrey C. Rathmell, Eric Jonasch, Brian I. Rini, W. Kimryn Rathmell, Kathryn E. Beckermann

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number1475
JournalCancers
Volume13
Issue number6
DOIs
StatePublished - Mar 2 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Keywords

  • Biomarkers
  • Immune checkpoint inhibitors
  • PD‐1
  • PD‐L1
  • Renal cell carcinoma

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