The 5-year survival rate for head and neck squamous cell carcinoma (HNSCC) is approximately 65%. In addition to radio-chemotherapy, immunotherapy is an approach in the treatment of advanced HNSCC. A better understanding of the immune context would allow personalized treatment by identifying patients who are best suited for different treatment options. In our discovery cohort, we evaluated the expression profiles of CMTM6, PD-L1, CTLA-4, and FOXP3 in 177 HNSCCs from Caucasian patients of all tumor stages and different treatment regimens, correlating marker expression in tumor and immune cells with outcomes. Patients with CMTM6high-expressing tumors had a longer overall survival regardless of treatment. This prognostic benefit of CMTM6 in HNSCC was validated in an independent cohort. Focusing on the in the discovery cohort (n = 177), a good predictive effect of CMTM6highexpression was seen in patients receiving radiotherapy (p= 0.07; log rank), but not in others. CMTM6 correlated with PD-L1, CTLA-4 and FOXP3 positivity, with patients possessing CMTM6high/FOXP3hightumors showing the longest survival regardless of treatment. In chemotherapy-treated patients, PD-L1 positivity was associated with longer progression-free survival (p< 0.05). In the 27 patients who received immunotherapy, gene expression analysis revealed lower levels ofCTLA-4andFOXP3with either partial or complete response to this treatment, while no effect was observed for CMTM6 or PD-L1. The combination of these immunomodulatory markers seems to be an interesting prognostic and predictive signature for HNSCC patients with the ability to optimize individualized treatments.
头颈部鳞状细胞癌（HNSCC）的五年生存率约为65%。除放化疗外，免疫疗法是治疗晚期HNSCC的一种重要手段。深入理解肿瘤免疫微环境有助于通过筛选最适合不同治疗方案的患者实现个体化治疗。在本研究的探索队列中，我们评估了177例涵盖所有肿瘤分期及不同治疗方案的欧洲裔HNSCC患者肿瘤组织中CMTM6、PD-L1、CTLA-4和FOXP3的表达谱，并将肿瘤细胞与免疫细胞中的标志物表达水平与临床结局进行关联分析。无论接受何种治疗，CMTM6高表达肿瘤患者的总生存期更长。CMTM6在HNSCC中的这一预后价值在独立队列中得到验证。聚焦探索队列（n=177）发现，CMTM6高表达在接受放疗的患者中显示出良好的预测效果（p=0.07；对数秩检验），但在其他治疗组中未观察到类似效应。CMTM6表达与PD-L1、CTLA-4及FOXP3阳性表达呈正相关，其中CMTM6高表达/FOXP3高表达患者无论接受何种治疗均表现出最长的生存期。在化疗患者中，PD-L1阳性表达与更长的无进展生存期相关（p<0.05）。在27例接受免疫治疗的患者中，基因表达分析显示对治疗产生部分或完全应答者的CTLA-4和FOXP3表达水平较低，而CMTM6或PD-L1未显示类似效应。这些免疫调节标志物的组合检测有望成为HNSCC患者预后评估和治疗预测的重要标志，为优化个体化治疗方案提供依据。
Identifying Predictive Biomarkers for Head and Neck Squamous Cell Carcinoma Response
肿瘤(癌症)患者之家