American Association for Cancer Research
00085472can163167-sup-173149_2_supp_4171403_9tdrcc.pptx (83.15 kB)

Supplementary Figure S1 from PD-1 Status in CD8+ T Cells Associates with Survival and Anti-PD-1 Therapeutic Outcomes in Head and Neck Cancer

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posted on 2023-03-31, 00:48 authored by Benjamin A. Kansy, Fernando Concha-Benavente, Raghvendra M. Srivastava, Hyun-Bae Jie, Gulidanna Shayan, Yu Lei, Jessica Moskovitz, Jennifer Moy, Jing Li, Sven Brandau, Stephan Lang, Nicole C. Schmitt, Gordon J. Freeman, William E. Gooding, David A. Clump, Robert L. Ferris

Supplementary Figure S1 shows identification of different subsets of PD1+ cells


National Institute of Health

University of Pittsburgh Cancer Institute



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.

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