Frontiers in Immunology (Jan 2022)
Analysis of Immunological Characteristics and Genomic Alterations in HPV-Positive Oropharyngeal Squamous Cell Carcinoma Based on PD-L1 Expression
- Sheng-ming Xu,
- Sheng-ming Xu,
- Sheng-ming Xu,
- Sheng-ming Xu,
- Chao-ji Shi,
- Chao-ji Shi,
- Chao-ji Shi,
- Chao-ji Shi,
- Rong-hui Xia,
- Rong-hui Xia,
- Rong-hui Xia,
- Rong-hui Xia,
- Li-zhen Wang,
- Li-zhen Wang,
- Li-zhen Wang,
- Li-zhen Wang,
- Zhen Tian,
- Zhen Tian,
- Zhen Tian,
- Zhen Tian,
- Wei-min Ye,
- Wei-min Ye,
- Wei-min Ye,
- Wei-min Ye,
- Liu Liu,
- Liu Liu,
- Liu Liu,
- Liu Liu,
- Shu-li Liu,
- Shu-li Liu,
- Shu-li Liu,
- Shu-li Liu,
- Chun-ye Zhang,
- Chun-ye Zhang,
- Chun-ye Zhang,
- Chun-ye Zhang,
- Yu-hua Hu,
- Yu-hua Hu,
- Yu-hua Hu,
- Yu-hua Hu,
- Rong Zhou,
- Rong Zhou,
- Rong Zhou,
- Rong Zhou,
- Yong Han,
- Yong Han,
- Yong Han,
- Yong Han,
- Yu Wang,
- Yu Wang,
- Yu Wang,
- Yu Wang,
- Zhi-yuan Zhang,
- Zhi-yuan Zhang,
- Zhi-yuan Zhang,
- Zhi-yuan Zhang,
- Jiang Li,
- Jiang Li,
- Jiang Li,
- Jiang Li
Affiliations
- Sheng-ming Xu
- Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Sheng-ming Xu
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Sheng-ming Xu
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- Sheng-ming Xu
- Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
- Chao-ji Shi
- Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Chao-ji Shi
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Chao-ji Shi
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- Chao-ji Shi
- Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
- Rong-hui Xia
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Rong-hui Xia
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- Rong-hui Xia
- Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
- Rong-hui Xia
- Department of Oral Pathology, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Li-zhen Wang
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Li-zhen Wang
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- Li-zhen Wang
- Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
- Li-zhen Wang
- Department of Oral Pathology, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Zhen Tian
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Zhen Tian
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- Zhen Tian
- Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
- Zhen Tian
- Department of Oral Pathology, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Wei-min Ye
- Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Wei-min Ye
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Wei-min Ye
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- Wei-min Ye
- Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
- Liu Liu
- Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Liu Liu
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Liu Liu
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- Liu Liu
- Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
- Shu-li Liu
- Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shu-li Liu
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Shu-li Liu
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- Shu-li Liu
- Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
- Chun-ye Zhang
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Chun-ye Zhang
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- Chun-ye Zhang
- Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
- Chun-ye Zhang
- Department of Oral Pathology, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Yu-hua Hu
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Yu-hua Hu
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- Yu-hua Hu
- Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
- Yu-hua Hu
- Department of Oral Pathology, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Rong Zhou
- Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Rong Zhou
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Rong Zhou
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- Rong Zhou
- Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
- Yong Han
- Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Yong Han
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Yong Han
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- Yong Han
- Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
- Yu Wang
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Yu Wang
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- Yu Wang
- Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
- Yu Wang
- Department of Oral Pathology, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Zhi-yuan Zhang
- Department of Oral and Maxillofacial-Head Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Zhi-yuan Zhang
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Zhi-yuan Zhang
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- Zhi-yuan Zhang
- Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
- Jiang Li
- National Clinical Research Center for Oral Diseases, National Center for Stomatology, Shanghai, China
- Jiang Li
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China
- Jiang Li
- Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, China
- Jiang Li
- Department of Oral Pathology, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- DOI
- https://doi.org/10.3389/fimmu.2021.798424
- Journal volume & issue
-
Vol. 12
Abstract
Programmed death-ligand 1 (PD-L1) expression has been approved as an immune checkpoint inhibitor (ICI) response predictive biomarker; however, the clinicopathological and molecular features of HPV-positive oropharyngeal squamous cell carcinoma [HPV(+)OPSCC] based on PD-L1 expression are not well studied. We aimed to characterize clinicopathological, tumor immune microenvironmental, and molecular features of HPV(+)OPSCC with different PD-L1 expression scored by combined positive score (CPS). A total of 112 cases were collected from 2008-2021 and received PD-L1 and CD8 immunohistochemistry (IHC) staining. 71 samples received DNA sequencing out of which 32 samples received RNA sequencing for immune-related gene alterations or expression analysis. The 32 samples were also subjected to analysis of CD20, CD4, CD8, CD68, Foxp3 and P16 by multiplex immunofluorescence (mIF) staining, and the immune markers were evaluated in the tumor body (TB), tumor margin (TM) and normal stroma (NS) regions separately. Our results showed that of 112 HPV(+)OPSCC tumors, high(CPS≥20), intermediate(1≤CPS<20), and low(CPS<1) PD-L1 expression was seen in 29.5%, 43.8% and 26.8% cases respectively. Non-smoking patients and patients with tumors occurring at the tonsils or having rich lymphocytes infiltration had significantly higher PD-L1 expression. Patients with CPS≥20 had significantly higher tumor mutation burden (TMB, p=0.0058), and PD-L1 expression correlated significantly with CD8+ T cells infiltration, which were ample in tumor regions than in NS in mIF. CD20+, CD4+, CD68+, Foxp3+CD4+ cells were demonstrated to infiltrate higher in TM while CD20+ and CD68+ cells were also enriched in NS and TB regions respectively. However, none of them showed correlations with PD-L1 expression. ARID1A, STK11 alterations were enriched in the low PD-L1 group significantly, while anti-viral immune associated APOBEC mutation signature and immune-related genes expression such as XCL1 and IL11 were positively associated with PD-L1 expression (p<0.05). This is a comprehensive investigation revealing immune and molecular features of HPV(+)OPSCC based on PD-L1 expression. Our study suggested that 73.2% of HPV(+)OPSCC patients may benefit from immunotherapy, and high PD-L1 expression reflects immune-active status of HPV(+)OPSCC accompanied by higher immune effect factors such as TMB, CD8+ cytotoxic T cells and immune-related genomic alterations. Our study offers valuable information for understanding the immune features of HPV(+)OPSCC.
Keywords
