Cancers (Mar 2021)
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 Bordeaux,
- Shridar 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
Affiliations
- Eileen Shiuan
- Medical Scientist Training Program, Vanderbilt University, Nashville, TN 37232, USA
- Anupama Reddy
- Prism Bioanalytics, North Carolina Biotechnology Center, Morrisville, NC 27560, USA
- Stephanie O. Dudzinski
- Medical Scientist Training Program, Vanderbilt University, Nashville, TN 37232, USA
- Aaron R. Lim
- Medical Scientist Training Program, Vanderbilt University, Nashville, TN 37232, USA
- Ayaka Sugiura
- Medical Scientist Training Program, Vanderbilt University, Nashville, TN 37232, USA
- Rachel Hongo
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Kirsten Young
- Health Science Center, College of Medicine, The University of Tennessee, Memphis, TN 38163, USA
- Xian-De Liu
- Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Christof C. Smith
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
- Jamye O’Neal
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Kimberly B. Dahlman
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Renee McAlister
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Beiru Chen
- Navigate Biopharma Services, Inc., A Novartis Subsidiary, Carlsbad, CA 92008, USA
- Kristen Ruma
- Navigate Biopharma Services, Inc., A Novartis Subsidiary, Carlsbad, CA 92008, USA
- Nathan Roscoe
- Navigate Biopharma Services, Inc., A Novartis Subsidiary, Carlsbad, CA 92008, USA
- Jehovana Bender
- Navigate Biopharma Services, Inc., A Novartis Subsidiary, Carlsbad, CA 92008, USA
- Joolz Ward
- Thermo Fisher Scientific, Sacramento, CA 95605, USA
- Ju Young Kim
- Navigate Biopharma Services, Inc., A Novartis Subsidiary, Carlsbad, CA 92008, USA
- Christine Vaupel
- Navigate Biopharma Services, Inc., A Novartis Subsidiary, Carlsbad, CA 92008, USA
- Jennifer Bordeaux
- Navigate Biopharma Services, Inc., A Novartis Subsidiary, Carlsbad, CA 92008, USA
- Shridar Ganesan
- Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA
- Tina M. Mayer
- Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA
- Gregory M. Riedlinger
- Department of Pathology, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA
- Benjamin G. Vincent
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA
- Nancy B. Davis
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Scott M. Haake
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Jeffrey C. Rathmell
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, TN 37232, USA
- Eric Jonasch
- Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
- Brian I. Rini
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- W. Kimryn Rathmell
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Kathryn E. Beckermann
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- DOI
- https://doi.org/10.3390/cancers13061475
- Journal volume & issue
-
Vol. 13,
no. 6
p. 1475
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 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%, 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 biomarker development in RCC, future studies will benefit from integrated analysis of multiple molecular platforms and prospective validation.
Keywords
