Combinatorial biomarker for predicting outcomes to anti-PD-1 therapy in patients with metastatic clear cell renal cell carcinoma

Julie Stein Deutsch; Evan J. Lipson; Ludmila Danilova; Suzanne L. Topalian; Jaroslaw Jedrych; Ezra Baraban; Yasser Ged; Nirmish Singla; Toni K. Choueiri; Saurabh Gupta; Robert J. Motzer; David McDermott; Sabina Signoretti; Michael Atkins; Janis M. Taube

doi:10.1016/j.xcrm.2023.100947

Combinatorial biomarker for predicting outcomes to anti-PD-1 therapy in patients with metastatic clear cell renal cell carcinoma

Julie Stein Deutsch, Evan J. Lipson, Ludmila Danilova, Suzanne L. Topalian, Jaroslaw Jedrych, Ezra Baraban, Yasser Ged, Nirmish Singla, Toni K. Choueiri, Saurabh Gupta, Robert J. Motzer, David McDermott, Sabina Signoretti, Michael Atkins, Janis M. Taube

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

With a rapidly developing immunotherapeutic landscape for patients with metastatic clear cell renal cell carcinoma, biomarkers of efficacy are highly desirable to guide treatment strategy. Hematoxylin and eosin (H&E)-stained slides are inexpensive and widely available in pathology laboratories, including in resource-poor settings. Here, H&E scoring of tumor-infiltrating immune cells (TIL^plus) in pre-treatment tumor specimens using light microscopy is associated with improved overall survival (OS) in three independent cohorts of patients receiving immune checkpoint blockade. Necrosis score alone does not associate with OS; however, necrosis modifies the predictive effect of TIL^plus, a finding that has broad translational relevance for tissue-based biomarker development. PBRM1 mutational status is combined with H&E scores to further refine outcome predictions (OS, p = 0.007, and objective response, p = 0.04). These findings bring H&E assessment to the fore for biomarker development in future prospective, randomized trials, and emerging multi-omics classifiers.

Original language	English (US)
Article number	100947
Journal	Cell Reports Medicine
Volume	4
Issue number	2
DOIs	https://doi.org/10.1016/j.xcrm.2023.100947
State	Published - Feb 21 2023

Keywords

H&E
PBRM1
PD-1
RCC
TIL
biomarker
immunotherapy
irPRC
necrosis
pathologic response

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.xcrm.2023.100947

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Deutsch, J. S., Lipson, E. J., Danilova, L., Topalian, S. L., Jedrych, J., Baraban, E., Ged, Y., Singla, N., Choueiri, T. K., Gupta, S., Motzer, R. J., McDermott, D., Signoretti, S., Atkins, M., & Taube, J. M. (2023). Combinatorial biomarker for predicting outcomes to anti-PD-1 therapy in patients with metastatic clear cell renal cell carcinoma. Cell Reports Medicine, 4(2), Article 100947. https://doi.org/10.1016/j.xcrm.2023.100947

Deutsch, JS , Lipson, EJ , Danilova, L , Topalian, SL , Jedrych, J , Baraban, E , Ged, Y , Singla, N, Choueiri, TK, Gupta, S, Motzer, RJ, McDermott, D, Signoretti, S, Atkins, M & Taube, JM 2023, 'Combinatorial biomarker for predicting outcomes to anti-PD-1 therapy in patients with metastatic clear cell renal cell carcinoma', Cell Reports Medicine, vol. 4, no. 2, 100947. https://doi.org/10.1016/j.xcrm.2023.100947

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title = "Combinatorial biomarker for predicting outcomes to anti-PD-1 therapy in patients with metastatic clear cell renal cell carcinoma",

abstract = "With a rapidly developing immunotherapeutic landscape for patients with metastatic clear cell renal cell carcinoma, biomarkers of efficacy are highly desirable to guide treatment strategy. Hematoxylin and eosin (H&E)-stained slides are inexpensive and widely available in pathology laboratories, including in resource-poor settings. Here, H&E scoring of tumor-infiltrating immune cells (TILplus) in pre-treatment tumor specimens using light microscopy is associated with improved overall survival (OS) in three independent cohorts of patients receiving immune checkpoint blockade. Necrosis score alone does not associate with OS; however, necrosis modifies the predictive effect of TILplus, a finding that has broad translational relevance for tissue-based biomarker development. PBRM1 mutational status is combined with H&E scores to further refine outcome predictions (OS, p = 0.007, and objective response, p = 0.04). These findings bring H&E assessment to the fore for biomarker development in future prospective, randomized trials, and emerging multi-omics classifiers.",

keywords = "H&E, PBRM1, PD-1, RCC, TIL, biomarker, immunotherapy, irPRC, necrosis, pathologic response",

author = "Deutsch, {Julie Stein} and Lipson, {Evan J.} and Ludmila Danilova and Topalian, {Suzanne L.} and Jaroslaw Jedrych and Ezra Baraban and Yasser Ged and Nirmish Singla and Choueiri, {Toni K.} and Saurabh Gupta and Motzer, {Robert J.} and David McDermott and Sabina Signoretti and Michael Atkins and Taube, {Janis M.}",

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AU - Deutsch, Julie Stein

AU - Lipson, Evan J.

AU - Danilova, Ludmila

AU - Topalian, Suzanne L.

AU - Jedrych, Jaroslaw

AU - Baraban, Ezra

AU - Ged, Yasser

AU - Singla, Nirmish

AU - Choueiri, Toni K.

AU - Gupta, Saurabh

AU - Motzer, Robert J.

AU - McDermott, David

AU - Signoretti, Sabina

AU - Atkins, Michael

AU - Taube, Janis M.

PY - 2023/2/21

Y1 - 2023/2/21

N2 - With a rapidly developing immunotherapeutic landscape for patients with metastatic clear cell renal cell carcinoma, biomarkers of efficacy are highly desirable to guide treatment strategy. Hematoxylin and eosin (H&E)-stained slides are inexpensive and widely available in pathology laboratories, including in resource-poor settings. Here, H&E scoring of tumor-infiltrating immune cells (TILplus) in pre-treatment tumor specimens using light microscopy is associated with improved overall survival (OS) in three independent cohorts of patients receiving immune checkpoint blockade. Necrosis score alone does not associate with OS; however, necrosis modifies the predictive effect of TILplus, a finding that has broad translational relevance for tissue-based biomarker development. PBRM1 mutational status is combined with H&E scores to further refine outcome predictions (OS, p = 0.007, and objective response, p = 0.04). These findings bring H&E assessment to the fore for biomarker development in future prospective, randomized trials, and emerging multi-omics classifiers.

AB - With a rapidly developing immunotherapeutic landscape for patients with metastatic clear cell renal cell carcinoma, biomarkers of efficacy are highly desirable to guide treatment strategy. Hematoxylin and eosin (H&E)-stained slides are inexpensive and widely available in pathology laboratories, including in resource-poor settings. Here, H&E scoring of tumor-infiltrating immune cells (TILplus) in pre-treatment tumor specimens using light microscopy is associated with improved overall survival (OS) in three independent cohorts of patients receiving immune checkpoint blockade. Necrosis score alone does not associate with OS; however, necrosis modifies the predictive effect of TILplus, a finding that has broad translational relevance for tissue-based biomarker development. PBRM1 mutational status is combined with H&E scores to further refine outcome predictions (OS, p = 0.007, and objective response, p = 0.04). These findings bring H&E assessment to the fore for biomarker development in future prospective, randomized trials, and emerging multi-omics classifiers.

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KW - necrosis

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Combinatorial biomarker for predicting outcomes to anti-PD-1 therapy in patients with metastatic clear cell renal cell carcinoma

Abstract

Keywords

ASJC Scopus subject areas

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