Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Zhang S

PROVIDER: S-EPMC8019230 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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

Zhang Siwei S Wang Bozhi B Ma Fen F Tong Fangjia F Yan Bingqing B Liu Tianyang T Xie Huanhuan H Song Lianhao L Yu Siyang S Wei Lanlan L

Cancer science 20210225 4

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 fro ...[more]

PMID: 33529452

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Project description:Human papillomavirus (HPV) is an accepted cause of head and neck squamous cell carcinoma (HNSCC), and patients with HPV-associated HNSCC have a favorable prognosis. Currently, there is no general guidance on the most appropriate biomarkers for clinical assessment of HPV in these malignancies. We compared PCR-based and serologic HPV assays, as well as p16 immunohistochemistry, individually and in combination in a single population-based study to assess their associations with overall survival among patients with HNSCC, and thus their potential value as biomarkers. HPV16 serology was determined for 488 patients; immunohistochemical detection of p16 expression in tumors was conducted in a subset of 233 cases, and PCR-based methods to assess the presence of HPV16 DNA in a subset of 179 cases of tumors. Considering each biomarker individually in the subset of patients studied for all endpoints, seropositivity for the E6 and E7 proteins was significantly associated with enhanced all-cause survival in oropharyngeal disease [HR(E6/E7+) = 0.1, 95% confidence interval (CI) = 0.02-0.3]. Neither the presence of HPV16 DNA nor p16 immunostaining was associated with significant enhanced overall survival in oropharyngeal disease (HR(DNA) = 0.9, 95% CI = 0.3-2.9; HR(p16) = 0.3, 95% CI = 0.1-1.1). However, the combination of HPV-positive DNA and E6 or E7 serology was associated with enhanced overall survival in oropharyngeal disease (HR(DNA+/E6/E7+) = 0.1, 95% CI = 0.02-1.0), whereas E6/E7 seronegative patients with evidence of HPV in tumor DNA did not show any evidence of favorable survival (HR(DNA+/E6-/E7-) = 3.4, 95% CI = 0.6-18.1). Furthermore, patients with p16 staining and E6 or E7 seropositivity had favorable survival from oropharyngeal disease (HR(p16+/E6/E7+) = 0.1, 95% CI = 0.02-0.4), whereas patients who were p16 positive and E6/E7 seronegative had significantly increased hazard of all causes of death (HR(p16+/E6-/E7-) = 3.1, 95% CI = 1.2-7.7). A stronger association of HPV presence with prognosis (assessed by all-cause survival) is observed when "HPV-associated" HNSCC is defined using tumor status (HPV DNA status or P16) and HPV E6/E7 serology in combination rather using tumor HPV status alone.

Project description:ObjectiveWe investigated the correlations between cyclin-dependent kinase 4/6 (CDK4/6) levels and human papillomavirus (HPV) infection state in head and neck squamous cell cancer (HNSCC). The aim was to explore the potential value of CDK4/6 inhibitors in the treatment of HNSCC.MethodsMultiomic sequencing data for HNSCC were obtained from The Cancer Genome Atlas (TCGA), and the mRNA levels and copy number variations (CNVs) of CDK4 and CDK6 were strictly analyzed. Overall survival (OS) curves were produced using the Kaplan-Meier method, and survival differences between groups were assessed by the log-rank test. Next, gene set enrichment analysis (GSEA) was applied to interrogate CDK4/6-associated molecular pathways in HPV-positive (HPV+) and HPV-negative (HPV-) HNSCC. Last, lymphoid cell infiltrates in each type of HNSCC were explored, and the correlations between CDK4/6 expression and lymphoid infiltrates were explored by Tumor Immune Estimation Resource (TIMER) analysis.ResultsOverexpression of either CDK6 or CDK4 was not a relevant factor for OS in HPV- HNSCC (CDK6: top 40%vs. bottom 40%, P=0.885; CDK4: top 40% vs. bottom 40%, P=0.267). In HPV+ HNSCC, CDK6 but not CDK4 was a relevant factor for OS (CDK6: top 40% vs. bottom 40%, P=0.002; CDK4: top 40% vs. bottom 40%, P=0.452). GSEA found that overexpressed CDK6 in HPV+ HNSCC inhibited pathways involved in the tumor immune response, suggesting its roles in antitumor immunity. TIMER analysis results revealed that CDK6 but not CDK4 accumulation was negatively correlated with the number of tumor-infiltrating lymphocytes specific for HPV+ HNSCC, which led to tumor response suppression.ConclusionsCDK6, but not CDK4, is a poor prognostic marker specific in HPV+ HNSCC patients. Overexpressed CDK6 might stimulate tumor progression by suppressing lymphocytes infiltration independent of its kinase activity. Only abrogating its kinase activity using current CDK4/6 inhibitors was not enough to block its tumor promotion function.

Project description:Background: Immunotherapy has become the new standard of care for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC), and PD-L1 is a widely used biomarker for immunotherapeutic response. However, PD-L1 expression in most cancer patients is low, and alternative biomarkers used to screen the population benefiting from immunotherapy are still being explored. Tumor microenvironment (TME), especially tumor immune-infiltrating cells, regulates the body's immunity, affects the tumor growth, and is expected to be a promising biomarker for immunotherapy. Purpose: This article mainly discussed how the immune-infiltrating cell patterns impacted immunity, thereby affecting HNSCC patients' prognosis. Method: The immune-infiltrating cell profile was generated by the CIBERSORT algorithm based on the transcriptomic data of HNSCC. Consensus clustering was used to divide groups with different immune cell infiltration patterns. Differentially expressed genes (DEGs) obtained from the high and low immune cell infiltration (ICI) groups were subjected to Kaplan-Meier and univariate Cox analysis. Significant prognosis-related DEGs were involved in the construction of a prognostic signature using multivariate Cox analysis. Results: In our study, 408 DEGs were obtained from high- and low-ICI groups, and 59 of them were significantly associated with overall survival (OS). Stepwise multivariate Cox analysis developed a 16-gene prognostic signature, which could distinguish favorable and poor prognosis of HNSCC patients. An ROC curve and nomogram verified the sensitivity and accuracy of the prognostic signature. The AUC values for 1 year, 2 years, and 3 years were 0.712, 0.703, and 0.700, respectively. TCGA-HNSCC cohort, GSE65858 cohort, and an independent GSE41613 cohort proved a similar prognostic significance. Notably, the prognostic signature distinguished the expression of promising immune inhibitory receptors (IRs) well and could predict the response to immunotherapy. Conclusion: We established a tumor immune cell infiltration (TICI)-based 16-gene signature, which could distinguish patients with different prognosis and help predict the response to immunotherapy.

Dataset Information

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

Publications

Characteristics of B lymphocyte infiltration in HPV<sup>+</sup> head and neck squamous cell carcinoma.

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