TY - JOUR
T1 - Clinical features and multiplatform molecular analysis assist in understanding patient response to anti‐pd‐1/pd‐l1 in renal cell carcinoma
AU - Shiuan, Eileen
AU - Reddy, Anupama
AU - Dudzinski, Stephanie O.
AU - Lim, Aaron R.
AU - Sugiura, Ayaka
AU - Hongo, Rachel
AU - Young, Kirsten
AU - Liu, Xian De
AU - Smith, Christof C.
AU - O’neal, Jamye
AU - Dahlman, Kimberly B.
AU - McAlister, Renee
AU - Chen, Beiru
AU - Ruma, Kristen
AU - Roscoe, Nathan
AU - Bender, Jehovana
AU - Ward, Joolz
AU - Kim, Ju Young
AU - Vaupel, Christine
AU - Bordeaux, Jennifer
AU - Ganesan, Shridar
AU - Mayer, Tina M.
AU - Riedlinger, Gregory M.
AU - Vincent, Benjamin G.
AU - Davis, Nancy B.
AU - Haake, Scott M.
AU - Rathmell, Jeffrey C.
AU - Jonasch, Eric
AU - Rini, Brian I.
AU - Kimryn Rathmell, W.
AU - Beckermann, Kathryn E.
N1 - Publisher Copyright:
© 2021 by the authors. Li-censee MDPI, Basel, Switzerland.
PY - 2021/3/2
Y1 - 2021/3/2
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Immune checkpoint inhibitors
KW - PD‐1
KW - PD‐L1
KW - Renal cell carcinoma
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U2 - 10.3390/cancers13061475
DO - 10.3390/cancers13061475
M3 - Article
C2 - 33806963
AN - SCOPUS:85102809666
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 6
M1 - 1475
ER -