Chen Jun, Meng Xiangchao, Zhou Qinyi, Feng Jialin, Zheng Wenjie, Wang Zhuoying, Wang Jiadong, Wang You
Head and Neck Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Bone and Joint Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Onco Targets Ther. 2020 Jun 22;13:5869-5877. doi: 10.2147/OTT.S248958. eCollection 2020.
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).
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.
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.
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.
CXCR5阳性（CXCR5）肿瘤细胞浸润在不同类型癌症中具有不同的预后价值。本研究旨在评估CXCR5细胞浸润在头颈部鳞状细胞癌（HNSCC）中的作用。
本研究纳入两个患者队列：癌症基因组图谱队列（TCGA，n = 472）和仁济医院队列（RJHC，n = 201）。分别对TCGA和RJHC队列分析CXCR5相关mRNA和CXCR5 +细胞浸润情况。然后，我们从总生存期和免疫微环境方面评估CXCR5 mRNA与CXCR5细胞浸润之间的相关性。
在TCGA和RJHC队列中，5年总生存率分别与高CXCR5 mRNA表达和CXCR5细胞浸润显著相关（p < 0.01），即使在调整混杂因素后也是如此。此外，高CXCR5 mRNA表达与更多的CD4 T细胞、CD8 T细胞、浆细胞相关，而与树突状细胞较少相关。高CXCR5 mRNA表达还与细胞毒性IFNG、TNFSF11（RANKL）、GZMA、GZMB、GZMK、GZMM和PRF1的表达增加以及免疫抑制基因PDCD1（PD - 1）、CD274（PD - L1）、CTLA4、LAG3、HAVCR2（TIM - 3）、BTLA和TIGIT的表达增加相关。
肿瘤内CXCR5表达高的HNSCC患者比肿瘤内CXCR5表达低的患者预后更好。此外，CXCR5细胞浸润可作为独立的预后生物标志物或潜在的治疗靶点。CXCR5细胞的存在对头颈部癌症中免疫细胞的浸润有影响，这与其他癌症类型的报道不同。需要进一步的随机对照试验或纳入更多患者的研究来验证我们的结果。
