학술논문
Chemoradiotherapy-induced upregulation of PD-1 antagonizes immunity to HPV-related oropharyngeal cancer.
Document Type
Academic Journal
Author
Parikh F; Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York.; Duluc D; Baylor Institute of Immunology, Dallas, Texas.; Imai N; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.; Clark A; Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York.; Misiukiewicz K; Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, New York.; Bonomi M; Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, New York.; Gupta V; Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York.; Patsias A; Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York.; Parides M; Health Evidence and Policy, Program, Icahn School of Medicine at Mount Sinai, New York, New York.; Demicco EG; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.; Zhang DY; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.; Kim-Schulze S; Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, New York. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.; Kao J; Department of Radiation Oncology, Good Samaritan Hospital Medical Center, West Islip, New York.; Gnjatic S; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.; Oh S; Baylor Institute of Immunology, Dallas, Texas.; Posner MR; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York. Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, New York.; Sikora AG; Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York. andrew.sikora@BCM.edu.
Source
Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE
Subject
Language
English
Abstract
While viral antigens in human papillomavirus (HPV)-related oropharyngeal cancer (HPVOPC) are attractive targets for immunotherapy, the effects of existing standard-of-care therapies on immune responses to HPV are poorly understood. We serially sampled blood from patients with stage III-IV oropharyngeal cancer undergoing concomitant chemoradiotherapy with or without induction chemotherapy. Circulating immunocytes including CD4(+) and CD8(+) T cells, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) were profiled by flow cytometry. Antigen-specific T-cell responses were measured in response to HPV16 E6 and E7 peptide pools. The role of PD-1 signaling in treatment-related immunosuppression was functionally defined by performing HPV-specific T-cell assays in the presence of blocking antibody. While HPV-specific T-cell responses were present in 13 of 18 patients before treatment, 10 of 13 patients lost these responses within 3 months after chemoradiotherapy. Chemoradiotherapy decreased circulating T cells and markedly elevated MDSCs. PD-1 expression on CD4(+) T cells increased by nearly 2.5-fold after chemoradiotherapy, and ex vivo culture with PD-1-blocking antibody enhanced HPV-specific T-cell responses in 8 of 18 samples tested. Chemoradiotherapy suppresses circulating immune responses in patients with HPVOPC by unfavorably altering effector:suppressor immunocyte ratios and upregulating PD-1 expression on CD4(+) T cells. These data strongly support testing of PD-1-blocking agents in combination with standard-of-care chemoradiotherapy for HPVOPC.
(©2014 American Association for Cancer Research.)
(©2014 American Association for Cancer Research.)