Interferon-stimulated neutrophils as a predictor of immunotherapy response.

Autor:	Benguigui M; Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Rappaport Technion Integrated Cancer Center, Technion - Israel Institute of Technology, Haifa, Israel., Cooper TJ; Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Rappaport Technion Integrated Cancer Center, Technion - Israel Institute of Technology, Haifa, Israel; Department of Immunology, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel. Electronic address: timcooper@technion.ac.il., Kalkar P; Department of Human Biology, the Faculty of Natural Sciences, University of Haifa, Haifa, Israel., Schif-Zuck S; Department of Human Biology, the Faculty of Natural Sciences, University of Haifa, Haifa, Israel., Halaban R; Department of Dermatology, Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA., Bacchiocchi A; Department of Dermatology, Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA., Kamer I; Institute of Oncology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel., Deo A; Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Rappaport Technion Integrated Cancer Center, Technion - Israel Institute of Technology, Haifa, Israel., Manobla B; Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Rappaport Technion Integrated Cancer Center, Technion - Israel Institute of Technology, Haifa, Israel., Menachem R; Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Rappaport Technion Integrated Cancer Center, Technion - Israel Institute of Technology, Haifa, Israel., Haj-Shomaly J; Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Rappaport Technion Integrated Cancer Center, Technion - Israel Institute of Technology, Haifa, Israel., Vorontsova A; Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Rappaport Technion Integrated Cancer Center, Technion - Israel Institute of Technology, Haifa, Israel., Raviv Z; Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Rappaport Technion Integrated Cancer Center, Technion - Israel Institute of Technology, Haifa, Israel., Buxbaum C; Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Rappaport Technion Integrated Cancer Center, Technion - Israel Institute of Technology, Haifa, Israel., Christopoulos P; Department of Thoracic Oncology, Thoraxklinik and National Center for Tumor Diseases (NCT) at Heidelberg University Hospital, 69126 Heidelberg, Germany; Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, Germany., Bar J; Institute of Oncology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel., Lotem M; Department of Melanoma and Cancer Immunotherapy, Sharett Institute of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel., Sznol M; Department of Medicine, Division of Medical Oncology, Yale University School of Medicine, New Haven, CT, USA., Ariel A; Department of Human Biology, the Faculty of Natural Sciences, University of Haifa, Haifa, Israel., Shen-Orr SS; Rappaport Technion Integrated Cancer Center, Technion - Israel Institute of Technology, Haifa, Israel; Department of Immunology, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel., Shaked Y; Cell Biology and Cancer Science, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Rappaport Technion Integrated Cancer Center, Technion - Israel Institute of Technology, Haifa, Israel. Electronic address: yshaked@technion.ac.il.
Jazyk:	angličtina
Zdroj:	Cancer cell [Cancer Cell] 2024 Feb 12; Vol. 42 (2), pp. 253-265.e12. Date of Electronic Publication: 2024 Jan 04.
DOI:	10.1016/j.ccell.2023.12.005
Abstrakt:	Despite the remarkable success of anti-cancer immunotherapy, its effectiveness remains confined to a subset of patients-emphasizing the importance of predictive biomarkers in clinical decision-making and further mechanistic understanding of treatment response. Current biomarkers, however, lack the power required to accurately stratify patients. Here, we identify interferon-stimulated, Ly6E hi neutrophils as a blood-borne biomarker of anti-PD1 response in mice at baseline. Ly6E hi neutrophils are induced by tumor-intrinsic activation of the STING (stimulator of interferon genes) signaling pathway and possess the ability to directly sensitize otherwise non-responsive tumors to anti-PD1 therapy, in part through IL12b-dependent activation of cytotoxic T cells. By translating our pre-clinical findings to a cohort of patients with non-small cell lung cancer and melanoma (n = 109), and to public data (n = 1440), we demonstrate the ability of Ly6E hi neutrophils to predict immunotherapy response in humans with high accuracy (average AUC ≈ 0.9). Overall, our study identifies a functionally active biomarker for use in both mice and humans. Competing Interests: Declaration of interests M.B., T.J.C., and Y.S. declare that they hold a pending patent on the use of Ly6E(hi) neutrophils as a predictive biomarker for immunotherapy. P.C. serves on the advisory board to AstraZeneca, Boehringer Ingelheim, Chugai, Pfizer, Novartis, MSD, Takeda and Roche; receives research funds from AstraZeneca, Amgen, Boehringer Ingelheim, Novartis, Roche, and Takeda, receives speaker honoraria from AstraZeneca, Janssen, Novartis, Roche, Pfizer, Thermo Fisher, Takeda. J.B. serves as a consultant to AbbVie, Amgen, AstraZeneca, Bayer, MSD, Merck-Serono, Roche, Takeda, BMS, Medison, Pfizer, and received research funds from Immunai, OncoHost. M.S. holds equity in Actym, Adaptive Biotechnologies, Amphivena, Asher, Evolveimmune, Intensity, Nextcure, Normunity, Oncohost, Johnson and Johnson, Glaxo-Smith Kline; serves as a consultant to Adagene, Adaptimmune, Agenus, Alkermes, Alligator, Anaptys, Asher, Astra Zeneca, Biond, Biontech, Boston Pharmaceuticals, Bristol-Myers, Dragonfly, Evaxion, Evolveimmune, Genentech-Roche, Gilead, Glaxo Smith Kline, Ichnos, Idera, Immunocore, Incyte, Innate pharma, Iovance, iTEOS, Jazz Pharmaceuticals, Kadmon-Sanofi, Kanaph, Merck, Molecular Partners, Nextcure, Nimbus, Normunity, Numab, Ocellaris-Lilly, Oncohost, Ontario Institute for Cancer Research, Partner Therapeutics, Pfizer, Pierre-Fabre, PIO Therapeutics, Pliant, Regeneron, Rootpath, Rubius, Sapience, Simcha, Stcube, Sumitomo, Targovax, Teva, Turnstone, Verastem, Xilio. S.S.O. holds equity in CytoReason and serves as a consultant. Y.S. is a co-founder of OncoHost and RemedyCell, holds equity in these company and also serves as a consultant to both companies. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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