PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients
Authors
Hye Ryun Kim ; Sang-Jun Ha ; Min Hee Hong ; Su Jin Heo ; Yoon Woo Koh ; Eun Chang Choi ; Eun Kyung Kim ; Kyoung Ho Pyo ; Inkyung Jung ; Daekwan Seo ; Jaewoo Choi ; Byoung Chul Cho ; Sun Och Yoon
Adult ; Aged ; Aged, 80 and over ; B7-H1 Antigen/metabolism* ; CD8-Positive T-Lymphocytes/metabolism ; Carcinoma, Squamous Cell/immunology ; Carcinoma, Squamous Cell/metabolism* ; Carcinoma, Squamous Cell/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Head and Neck Neoplasms/immunology ; Head and Neck Neoplasms/metabolism* ; Head and Neck Neoplasms/pathology ; Humans ; Lymphocytes, Tumor-Infiltrating/metabolism* ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Analysis ; Young Adult
Abstract
To investigate the expression of programmed death-ligand 1 (PD-L1) and immune checkpoints and their prognostic value for resected head and neck squamous cell cancer (HNSCC). PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC), abundance of tumor-infiltrating lymphocytes (TILs), and expression of the immune checkpoints were investigated in 402 HNSCC patients. PD-L1 expression on TC and IC was categorized into four groups according to the percentage of PD-L1-positive cells. PD-L1 positivity was defined as ≥5% of cells based on immunohistochemistry. High PD-L1 expression on IC, but not TC, was an independent favorable prognostic factor for RFS and OS adjusted for age, gender, smoking, stage, and HPV. High frequencies of CD3+ or CD8+ TILs, Foxp3+ Tregs, and PD-1+ TILs were strongly associated with favorable prognosis. PD-L1 was exclusively expressed on either TC or IC. Transcriptome analysis demonstrated that IC3 expressed higher levels of the effector T cell markers than TC3, suggesting that PD-L1 expression is regulated via an adaptive IFNγ-mediated mechanism. High PD-L1 expression on IC, but not TC, and high abundance of PD-1+ T cells and Foxp3+ Tregs are favorable prognostic factors for resected HNSCC. This study highlights the importance of comprehensive assessment of both TC and IC.