Characteristics of B lymphocyte infiltration in HPV+ head and neck squamous cell carcinoma

• Published in: Cancer science Vol. 112; no. 4; pp. 1402 - 1416
• Main Authors: Zhang, Siwei, Wang, Bozhi, Ma, Fen, Tong, Fangjia, Yan, Bingqing, Liu, Tianyang, Xie, Huanhuan, Song, Lianhao, Yu, Siyang, Wei, Lanlan
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.04.2021; John Wiley and Sons Inc
• Subjects: Aged; Alphapapillomavirus - immunology; Antibodies; B lymphocyte subsets; B-Lymphocytes - immunology; Breast cancer; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - virology; CD19 antigen; CD27 antigen; CD38 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell cycle; chemokine; Chemokine CXCL13 - immunology; Chemokines; Colorectal cancer; CXCL13; CXCL13 protein; CXCR5 protein; Female; Gene expression; Genomes; Head & neck cancer; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - virology; head and neck squamous cell carcinoma; Human papillomavirus; human papillomavirus infection; Humans; Immune system; Immunofluorescence; Immunohistochemistry; Immunological memory; Infiltration; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Memory cells; Middle Aged; Original; ORIGINAL ARTICLES; Papillomavirus Infections - immunology; Papillomavirus Infections - virology; Plasma cells; Principal components analysis; Prognosis; Radiation therapy; Receptors, CXCR5 - immunology; Software; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - immunology; Squamous Cell Carcinoma of Head and Neck - virology; T lymphocytes; T lymphocytes; B lymphocyte subsets; chemokine; CXCL13; head and neck squamous cell carcinoma; human papillomavirus infection
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/cas.14834

Human papillomavirus (HPV) is an important etiological factor of head and neck squamous cell carcinoma (HNSCC). HPV+ HNSCC patients usually have a better prognosis, which probably results from the higher infiltration of B lymphocytes. This study was purposed to detect the infiltration of B lymphocyte subsets and the correlation between B lymphocyte subsets and the prognosis in HPV‐related HNSCC. In this study, 124 HPV+ and 513 HPV− HNSCC samples were obtained from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database for transcriptomic analysis. Infiltration of B lymphocytes subsets was detected with 7 HPV+ HNSCC and 13 HPV− HNSCC tissues through immunohistochemistry and immunofluorescence. One HPV− HNSCC sample was detected with single‐cell sequencing for chemokine analysis. In the results, the infiltration of plasma cells (CD19+CD38+) and memory B cells (MS4A1+CD27+) was higher in HPV+ HNSCC samples. High infiltration of plasma cells and memory B cells was related to a better prognosis. High density of B lymphocytes was positively correlated with high CXCL13 production mainly from CD4+ T lymphocytes in HNSCC. These results indicated that a high density of plasma cells and memory B cells could predict excellent prognosis. CD4+ T lymphocytes might affect B lymphocytes and their subsets through the CXCL13/CXCR5 axis in HNSCC. For the first time, we observed the infiltration and distribution of B lymphocyte subsets around HNSCC tissues by immunohistochemistry and immunofluorescence. We first discovered that the high infiltration of plasma cells (CD19+CD38+) and memory B cells (MS4A1+CD27+) in HPV+ HNSCC microenvironment was related to better prognosis, and CD4+ T cells could affect B lymphocyte infiltration through the CXCL13/CXCR5 axis.