@article{cffd168d05ad4f9e876b44d082fc28e5,
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.}",
note = "Funding Information: This work was supported by The Mark Foundation for Cancer Research (to J.M.T., S.L.T., and E.J.L.), Bristol-Myers Squibb (to J.M.T., E.J.L., and S.L.T.), Sidney Kimmel Cancer Center Core Grant P30 CA006973 (to J.M.T., L.D., and E.J.L.), National Cancer Institute R01 CA142779 (to J.M.T. and S.L.T.), NIH T32 CA193145 (to J.S.D.), R50 CA243627 (to L.D.), Dana-Farber/Harvard Cancer Center Kidney SPORE 2P50CA101942-16 (to T.K.C. and D.M.), and Program 5P30CA006516-56 (to T.K.C.), the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, Pan Mass Challenge, Hinda and Arthur Marcus Fund, Loker Pinard Funds for Kidney Cancer Research at DFCI (to T.K.C.), and the Bloomberg∼Kimmel Institute for Cancer Immunotherapy (to J.M.T., L.D., and S.L.T.). Patients treated at Memorial Sloan Kettering Cancer Center were supported in part by Memorial Sloan Kettering Cancer Center Support Grant/Core Grant ( P30 CA008748 ). Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = feb,
day = "21",
doi = "10.1016/j.xcrm.2023.100947",
language = "English (US)",
volume = "4",
journal = "Cell Reports Medicine",
issn = "2666-3791",
publisher = "Cell Press",
number = "2",
}