LAG-3 expression on peripheral blood cells identifies patients with poorer outcomes after immune checkpoint blockade.

Autor:	Shen R; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Postow MA; Department of Medicine, Memorial Sloan Kettering Cancer Center New York, NY 10065, USA.; Weill Cornell Medical College, New York, NY 10065, USA., Adamow M; Immune Monitoring Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA., Arora A; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Hannum M; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Maher C; Department of Medicine, Memorial Sloan Kettering Cancer Center New York, NY 10065, USA.; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA., Wong P; Immune Monitoring Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA., Curran MA; Department of Immunology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA., Hollmann TJ; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA.; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Jia L; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Al-Ahmadie H; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Keegan N; Department of Medicine, Memorial Sloan Kettering Cancer Center New York, NY 10065, USA., Funt SA; Department of Medicine, Memorial Sloan Kettering Cancer Center New York, NY 10065, USA.; Weill Cornell Medical College, New York, NY 10065, USA., Iyer G; Department of Medicine, Memorial Sloan Kettering Cancer Center New York, NY 10065, USA.; Weill Cornell Medical College, New York, NY 10065, USA., Rosenberg JE; Department of Medicine, Memorial Sloan Kettering Cancer Center New York, NY 10065, USA.; Weill Cornell Medical College, New York, NY 10065, USA., Bajorin DF; Department of Medicine, Memorial Sloan Kettering Cancer Center New York, NY 10065, USA.; Weill Cornell Medical College, New York, NY 10065, USA., Chapman PB; Department of Medicine, Memorial Sloan Kettering Cancer Center New York, NY 10065, USA.; Weill Cornell Medical College, New York, NY 10065, USA., Shoushtari AN; Department of Medicine, Memorial Sloan Kettering Cancer Center New York, NY 10065, USA.; Weill Cornell Medical College, New York, NY 10065, USA., Betof AS; Department of Medicine, Memorial Sloan Kettering Cancer Center New York, NY 10065, USA.; Weill Cornell Medical College, New York, NY 10065, USA., Momtaz P; Department of Medicine, Memorial Sloan Kettering Cancer Center New York, NY 10065, USA.; Weill Cornell Medical College, New York, NY 10065, USA., Merghoub T; Department of Medicine, Memorial Sloan Kettering Cancer Center New York, NY 10065, USA.; Weill Cornell Medical College, New York, NY 10065, USA.; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA.; Swim Across America/Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Human Oncology Pathogenesis Program, Sloan Kettering Institute, New York, NY 10065, USA., Wolchok JD; Department of Medicine, Memorial Sloan Kettering Cancer Center New York, NY 10065, USA.; Weill Cornell Medical College, New York, NY 10065, USA.; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA.; Swim Across America/Ludwig Collaborative Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.; Human Oncology Pathogenesis Program, Sloan Kettering Institute, New York, NY 10065, USA., Panageas KS; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Callahan MK; Department of Medicine, Memorial Sloan Kettering Cancer Center New York, NY 10065, USA. callaham@mskcc.org.; Weill Cornell Medical College, New York, NY 10065, USA.; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2021 Aug 25; Vol. 13 (608).
DOI:	10.1126/scitranslmed.abf5107
Abstrakt:	Immune checkpoint blocking antibodies are a cornerstone in cancer treatment; however, they benefit only a subset of patients and biomarkers to guide immune checkpoint blockade (ICB) treatment choices are lacking. We designed this study to identify blood-based correlates of clinical outcome in ICB-treated patients. We performed immune profiling of 188 ICB-treated patients with melanoma using multiparametric flow cytometry to characterize immune cells in pretreatment peripheral blood. A supervised statistical learning approach was applied to a discovery cohort to classify phenotypes and determine their association with survival and treatment response. We identified three distinct immune phenotypes (immunotypes), defined in part by the presence of a LAG-3 + CD8 + T cell population. Patients with melanoma with a LAG + immunotype had poorer outcomes after ICB with a median survival of 22.2 months compared to 75.8 months for those with the LAG - immunotype ( P = 0.031). An independent cohort of 94 ICB-treated patients with urothelial carcinoma was used for validation where LAG + immunotype was significantly associated with response ( P = 0.007), survival ( P < 0.001), and progression-free survival ( P = 0.004). Multivariate Cox regression and stratified analyses further showed that the LAG + immunotype was an independent marker of outcome when compared to known clinical prognostic markers and previously described markers for the clinical activity of ICB, PD-L1, and tumor mutation burden. The pretreatment peripheral blood LAG + immunotype detects patients who are less likely to benefit from ICB and suggests a strategy for identifying actionable immune targets for further investigation. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
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