Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Int Immunopharmacol. 2020 Oct;87:106802. doi: 10.1016/j.intimp.2020.106802. Epub 2020 Jul 31.
Tumor-infiltrating immune cells (TICs) are involved in tumor progression and determine the prognosis. We investigated how TICs affect the prognosis and therapeutic effects of squamous cell carcinoma (SCC), which share common histological features and certain risk factors. The SCC data from The Cancer Genome Atlas (TCGA) and Gene expression Omnibus (GEO) databases were downloaded to evaluate the composition of TICs with the CIBERSORT algorithm. LASSO and Cox multivariate regression analyses were used to build a prognostic risk model. Chemotherapeutic and immunotherapeutic responses were compared between patients with SCC. A Gene set variation analysis (GSVA) was also performed to elucidate the mechanism. Naïve B cells and resting mast cells were selected to construct the prognostic model. According to these two immune cell subtypes, patients with SCC were divided into low- and high-risk groups. The low-risk group with high proportions of naïve B cells and resting mast cells had a better overall survival rate than the high-risk group and might benefit from immunotherapy and chemotherapy due to differences in the immune microenvironment. Activation of the Wnt signaling pathway was observed in the high-risk group. Based on the findings from the present study, the immune signature provides prognostic determinants of SCC and may be a biomarker to guide chemotherapy and immunotherapy. Wnt inhibitors may be attractive candidates for combination treatment in high-risk patients with SCC.
肿瘤浸润免疫细胞(TICs)参与肿瘤的进展,并决定预后。我们研究了 TICs 如何影响鳞状细胞癌(SCC)的预后和治疗效果,因为它们具有共同的组织学特征和某些危险因素。从 The Cancer Genome Atlas(TCGA)和 Gene expression Omnibus(GEO)数据库下载 SCC 数据,并用 CIBERSORT 算法评估 TICs 的组成。使用 LASSO 和 Cox 多变量回归分析构建预后风险模型。比较 SCC 患者的化疗和免疫治疗反应。还进行了基因集变异分析(GSVA)以阐明机制。选择幼稚 B 细胞和静止肥大细胞来构建预后模型。根据这两种免疫细胞亚型,将 SCC 患者分为低风险组和高风险组。幼稚 B 细胞和静止肥大细胞比例较高的低风险组的总生存率高于高风险组,并且由于免疫微环境的差异,可能受益于免疫治疗和化疗。在高风险组中观察到 Wnt 信号通路的激活。基于本研究的结果,免疫特征为 SCC 提供了预后决定因素,并且可能是指导化疗和免疫治疗的生物标志物。Wnt 抑制剂可能是高危 SCC 患者联合治疗的有吸引力的候选药物。