Fewer tumour-specific PD-1+CD8+ TILs in high-risk "Infiltrating" HPV- HNSCC

Ke Xu; You Fu; Yong Han; Ronghui Xia; Shengming Xu; Shengzhong Duan; Zhiyuan Zhang; Jiang Li

doi:10.1038/s41416-020-0966-8

Fewer tumour-specific PD-1⁺CD8⁺ TILs in high-risk "Infiltrating" HPV^- HNSCC

Br J Cancer. 2020 Sep;123(6):932-941. doi: 10.1038/s41416-020-0966-8. Epub 2020 Jul 3.

Authors

Ke Xu^#^{1

2}, You Fu^#^{1

2}, Yong Han^{1

2}, Ronghui Xia^{1

3}, Shengming Xu^{1

2}, Shengzhong Duan^{1

4}, Zhiyuan Zhang^{5

6}, Jiang Li^{7

8}

Affiliations

¹ Shanghai Key Laboratory of Stomatology, Shanghai, P.R. China.
² Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
³ Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
⁴ Laboratory of Oral Microbiology, Shanghai Research Institute of Stomatology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
⁵ Shanghai Key Laboratory of Stomatology, Shanghai, P.R. China. zhzhy@sjtu.edu.cn.
⁶ Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China. zhzhy@sjtu.edu.cn.
⁷ Shanghai Key Laboratory of Stomatology, Shanghai, P.R. China. lijiang182000@sjtu.edu.cn.
⁸ Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China. lijiang182000@sjtu.edu.cn.

^# Contributed equally.

Abstract

Background: The prognosis of HPV^- HNSCC was worse than that of HPV⁺ HNSCC. Analysis of tumours and tumour-infiltrating lymphocytes (TILs) may provide insight into the progression of HPV^- HNSCC.

Methods: The tumour and TIL phenotypic characteristics of 134 HNSCC specimens (HPV^- tumours were classified into "Infiltrating" and "Pushing" subtypes based on their different tumour nest configuration and prognosis) were retrospectively analysed. HNSCC data from the Cancer Genome Atlas (n = 263) were analysed for CD8α, HPV and overall survival (OS). A murine HNSCC model was used to verify the antitumour role of PD-1⁺CD8⁺ TILs.

Results: The "Infiltrating" HPV^- subtype showed shorter OS than the "Pushing" subtype. Moreover, there is a tendency from "Pushing" to "Infiltrating" subtype from the primary to the recurrent lesion. Different from total CD8⁺ TILs, tumour-specific PD-1⁺CD8⁺ TILs were fewer in invasive margin (IM) of "Infiltrating" HPV^- tumours. PD-1⁺CD8⁺ TILs recognised autologous HNSCC cells and showed stronger inhibition of tumour growth in a murine HNSCC model resistant to PD-1 blockade.

Conclusions: Coevolution of HPV^- HNSCC and TILs is characterised by an "Infiltrating" phenotype and less tumour-specific PD-1⁺CD8⁺ TILs, which may provide a framework for further translational studies and patient stratification.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD8-Positive T-Lymphocytes / immunology*
Disease Models, Animal
Female
Immune Checkpoint Inhibitors / therapeutic use
Lymphocytes, Tumor-Infiltrating / immunology*
Mice
Mice, Inbred C3H
Papillomaviridae / isolation & purification
Prognosis
Programmed Cell Death 1 Receptor / analysis*
Squamous Cell Carcinoma of Head and Neck / drug therapy
Squamous Cell Carcinoma of Head and Neck / immunology*
Squamous Cell Carcinoma of Head and Neck / mortality
Squamous Cell Carcinoma of Head and Neck / virology

Substances

Immune Checkpoint Inhibitors
Programmed Cell Death 1 Receptor