51. PD-1 Status in CD8 + T Cells Associates with Survival and Anti-PD-1 Therapeutic Outcomes in Head and Neck Cancer.
- Author
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Kansy BA, Concha-Benavente F, Srivastava RM, Jie HB, Shayan G, Lei Y, Moskovitz J, Moy J, Li J, Brandau S, Lang S, Schmitt NC, Freeman GJ, Gooding WE, Clump DA, and Ferris RL
- Subjects
- Animals, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Cells, Cultured, Disease Models, Animal, Disease-Free Survival, Gene Expression drug effects, Head and Neck Neoplasms complications, Head and Neck Neoplasms immunology, Humans, Interferon-gamma immunology, Interferon-gamma metabolism, Lymphocytes, Tumor-Infiltrating drug effects, Lymphocytes, Tumor-Infiltrating immunology, Lymphocytes, Tumor-Infiltrating metabolism, Mice, Inbred C57BL, Outcome Assessment, Health Care methods, Outcome Assessment, Health Care statistics & numerical data, Papillomavirus Infections complications, Papillomavirus Infections immunology, Prognosis, Programmed Cell Death 1 Receptor genetics, Programmed Cell Death 1 Receptor immunology, Proportional Hazards Models, Antibodies, Monoclonal therapeutic use, CD8-Positive T-Lymphocytes drug effects, Head and Neck Neoplasms drug therapy, Papillomavirus Infections drug therapy, Programmed Cell Death 1 Receptor antagonists & inhibitors
- Abstract
Improved understanding of expression of immune checkpoint receptors (ICR) on tumor-infiltrating lymphocytes (TIL) may facilitate more effective immunotherapy in head and neck cancer (HNC) patients. A higher frequency of PD-1
+ TIL has been reported in human papillomavirus (HPV)+ HNC patients, despite the role of PD-1 in T-cell exhaustion. This discordance led us to hypothesize that the extent of PD-1 expression more accurately defines T-cell function and prognostic impact, because PD-1high T cells may be more exhausted than PD-1low T cells and may influence clinical outcome and response to anti-PD-1 immunotherapy. In this study, PD-1 expression was indeed upregulated on HNC patient TIL, and the frequency of these PD-1+ TIL was higher in HPV+ patients ( P = 0.006), who nonetheless experienced significantly better clinical outcome. However, PD-1high CD8+ TILs were more frequent in HPV- patients and represented a more dysfunctional subset with compromised IFN-γ secretion. Moreover, HNC patients with higher frequencies of PD-1high CD8+ TIL showed significantly worse disease-free survival and higher hazard ratio for recurrence ( P < 0.001), while higher fractions of PD-1low T cells associated with HPV positivity and better outcome. In a murine HPV+ HNC model, anti-PD-1 mAb therapy differentially modulated PD-1high/low populations, and tumor rejection associated with loss of dysfunctional PD-1high CD8+ T cells and a significant increase in PD-1low TIL. Thus, the extent of PD-1 expression on CD8+ TIL provides a potential biomarker for anti-PD-1-based immunotherapy. Cancer Res; 77(22); 6353-64. ©2017 AACR ., (©2017 American Association for Cancer Research.)- Published
- 2017
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