title: PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients.
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.
authors.affiliation: Yonsei Cancer Center, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hye Ryun
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Life Science &Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Ha
authors.affiliation: Yonsei Cancer Center, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Hong
authors.affiliation: Yonsei Cancer Center, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Heo
authors.affiliation: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Yoon Woo
authors.initials: YW
authors.lastname: Koh
authors.affiliation: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Eun Chang
authors.initials: EC
authors.lastname: Choi
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: JE-UK Institute for Cancer Research, JEUK Co., Ltd., Gumi-City, Kyungbuk, Korea.
authors.forename: Kyoung Ho
authors.initials: KH
authors.lastname: Pyo
authors.affiliation: Department of Biostatistics and Medical Informatics, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Inkyung
authors.initials: I
authors.lastname: Jung
authors.affiliation: Severance Biomedical Science Institute, Yonsei University of College of Medicine, Seoul, Korea.
authors.forename: Daekwan
authors.initials: D
authors.lastname: Seo
authors.affiliation: Severance Biomedical Science Institute, Yonsei University of College of Medicine, Seoul, Korea.
authors.forename: Jaewoo
authors.initials: J
authors.lastname: Choi
authors.affiliation: Yonsei Cancer Center, Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea.|JE-UK Institute for Cancer Research, JEUK Co., Ltd., Gumi-City, Kyungbuk, Korea.
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Cho
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sun Och
authors.initials: SO
authors.lastname: Yoon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human