Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma
Autor: | Michael Alvarado, Iryna Lobach, Keyon Taravati, Katy K. Tsai, Mariela L. Pauli, Matthew F. Krummel, Priscila Munoz Sandoval, Miguel Hernandez Pampaloni, Adi Nosrati, Michael Rosenblum, Kimberly Loo, Lorenzo Nardo, Iris K. Gratz, Adil Daud, Robert H. Pierce, Robert Sanchez-Rodriguez, Alain Algazi, Jimmy Hwang |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Male Skin Neoplasms T cell Biopsy Programmed Cell Death 1 Receptor CD8-Positive T-Lymphocytes Antibodies Monoclonal Humanized Lymphocyte Activation Cohort Studies 03 medical and health sciences 0302 clinical medicine Immune system Lymphocytes Tumor-Infiltrating T-Lymphocyte Subsets Cell Line Tumor medicine Tumor Microenvironment Cytotoxic T cell Humans CTLA-4 Antigen Neoplasm Metastasis Melanoma Tumor microenvironment biology business.industry General Medicine medicine.disease Flow Cytometry Immune checkpoint 030104 developmental biology medicine.anatomical_structure Phenotype 030220 oncology & carcinogenesis Immune System Immunology Cancer research biology.protein Leukocyte Common Antigens Female Antibody Clinical Medicine business CD8 |
Zdroj: | The Journal of clinical investigation. 126(9) |
ISSN: | 1558-8238 |
Popis: | BACKGROUND. Immune checkpoint blockade is revolutionizing therapy for advanced cancer, but many patients do not respond to treatment. The identification of robust biomarkers that predict clinical response to specific checkpoint inhibitors is critical in order to stratify patients and to rationally select combinations in the context of an expanding array of therapeutic options. METHODS. We performed multiparameter flow cytometry on freshly isolated metastatic melanoma samples from 2 cohorts of 20 patients each prior to treatment and correlated the subsequent clinical response with the tumor immune phenotype. RESULTS. Increasing fractions of programmed cell death 1 high/cytotoxic T lymphocyte–associated protein 4 high (PD-1hiCTLA-4hi) cells within the tumor-infiltrating CD8+ T cell subset strongly correlated with response to therapy (RR) and progression-free survival (PFS). Functional analysis of these cells revealed a partially exhausted T cell phenotype. Assessment of metastatic lesions during anti–PD-1 therapy demonstrated a release of T cell exhaustion, as measured by an accumulation of highly activated CD8+ T cells within tumors, with no effect on Tregs. CONCLUSIONS. Our data suggest that the relative abundance of partially exhausted tumor-infiltrating CD8+ T cells predicts response to anti–PD-1 therapy. This information can be used to appropriately select patients with a high likelihood of achieving a clinical response to PD-1 pathway inhibition. FUNDING. This work was funded by a generous gift provided by Inga-Lill and David Amoroso as well as a generous gift provided by Stephen Juelsgaard and Lori Cook. |
Databáze: | OpenAIRE |
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