Effect of CXCR5-Positive Cell Infiltration on the Immune Contexture and Patient Prognosis in Head and Neck Squamous Cell Carcinoma

PURPOSE: CXCR5-positive (CXCR5(+)) tumor cell infiltration has different prognostic values in different types of cancer. The objective was to evaluate the effect of CXCR5(+) cell infiltration in head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: The study included two patient cohorts: The Cancer Genome Atlas cohort (TCGA, n = 472) and the Renji Hospital cohort (RJHC, n = 201). The TCGA and RJHC cohorts were analyzed for CXCR5-related mRNAs and CXCR5+ cell infiltration, respectively. We then evaluated the correlation between CXCR5 mRNA and CXCR5(+) cell infiltration in terms of overall survival and the immune contexture. RESULTS: The 5-year overall survival rate was significantly correlated with high CXCR5 mRNA expression and CXCR5(+) cell infiltration in the TCGA and RJHC cohorts, respectively (p < 0.01), even after adjusting for confounders. Moreover, high CXCR5 mRNA expression was associated with more CD4(+) T cells, CD8(+) T cells, plasma cells, and less dendritic cells. A high CXCR5 mRNA expression was also correlated with increased expression of cytotoxic IFNG, TNFSF11 (RANKL), GZMA, GZMB, GZMK, GZMM, and PRF1 and increased expression of the immunosuppressive gene PDCD1 (PD-1), CD274 (PD-L1), CTLA4, LAG3, HAVCR2 (TIM-3), BTLA, and TIGIT. CONCLUSION: HNSCC patients with a high intratumoral CXCR5 expression had a better prognosis than those with low intratumoral CXCR5 expression. Moreover, CXCR5(+) cell infiltration could be used as an independent prognostic biomarker or as a potential therapeutic target. The presence of CXCR5(+) cells affects the infiltration of immunocytes in head and neck cancer, differently from what was reported in other cancer types. Further randomized controlled trials or studies with more patients are needed to validate our results.