Wang Yuntao, Liu Yi, Li Xiaohua, Li Weiming, Xue Zhihong, He Xiaoqian, Xiong Weijie, He Lang, Bai Yifeng
Department of Oncology, The Fifth People's Hospital Affiliated to Chengdu University of Traditional Chinese Medicine the Second Clinical Medical College, Chengdu, China.
Wenjiang District People's Hospital of Chengdu City, Chengdu, China.
Front Pharmacol. 2022 May 4;13:875149. doi: 10.3389/fphar.2022.875149. eCollection 2022.
: Lung cancer has the highest morbidity and mortality rate among types of malignant tumors, and as such, research into prolonging the survival time of patients is vital. The emergence of immune checkpoint inhibitors (ICIs) has greatly improved the survival of patients with non-small cell lung cancer (NSCLC), however, the lack of effective biomarkers to predict the prognosis of immunotherapy has made it difficult to maximize the benefits. T cell receptor (TCR) is one of the most important components for recognizing tumor cells, and with this study we aim to clarify the relationship between TCR coexpression and the prognosis of NSCLC patients receiving immunotherapy. : Univariate COX regression, logistics regression, and KM survival analysis were used to evaluate the relationship between TCR coexpression and the prognosis of immunotherapy. Additionally, CIBERSORT, Gene Set Enrichment Analysis (GSEA), and single-sample GSEA (ssGSEA) algorithms were used to evaluate the tumor immune microenvironment (TIME) of NSCLC patients. : Univariate Cox regression analysis showed that the TCR coexpression signature can be used as a clinical prognostic indicator for NSCLC patients receiving immunotherapy ( = 0.0205). In addition, those in the NSCLC group with a high TCR coexpression signature had significantly improved progression-free survival (PFS) ( = 0.014). In the ICI treatment cohort (GSE35640). In addition, there was a high infiltration of CD8+T cells, activated memory CD4+T cells, and M1 macrophages in the TIME of those with a high TCR coexpression signature. The results of pathway enrichment analysis showed that patients with a high TCR coexpression signature had significantly activated signal pathways such as lymphocyte proliferation and activation, chemokine binding, and inflammatory cytokine production. Also, we found that patients with a high TCR coexpression signature had an elevated T cell inflammation gene expression profile (GEP). : We show that the TCR coexpression signature may be useful as a new biomarker for the prognosis of NSCLC patients undergoing immunotherapy, with high signatures indicating better treatment response. Additionally, we found that patients with a high TCR coexpression signature had tumor immune microenvironments with beneficial anti-tumor characteristics.
肺癌在恶性肿瘤类型中发病率和死亡率最高，因此，研究延长患者生存时间至关重要。免疫检查点抑制剂（ICI）的出现极大地提高了非小细胞肺癌（NSCLC）患者的生存率，然而，缺乏有效的生物标志物来预测免疫治疗的预后使得难以最大化获益。T细胞受体（TCR）是识别肿瘤细胞的最重要成分之一，本研究旨在阐明TCR共表达与接受免疫治疗的NSCLC患者预后之间的关系。：采用单因素COX回归、逻辑回归和KM生存分析来评估TCR共表达与免疫治疗预后之间的关系。此外，使用CIBERSORT、基因集富集分析（GSEA）和单样本GSEA（ssGSEA）算法来评估NSCLC患者的肿瘤免疫微环境（TIME）。：单因素Cox回归分析表明，TCR共表达特征可作为接受免疫治疗的NSCLC患者的临床预后指标（=0.0205）。此外，NSCLC组中TCR共表达特征高的患者无进展生存期（PFS）显著改善（=0.014）。在ICI治疗队列（GSE35640）中。此外，TCR共表达特征高的患者的TIME中CD8 + T细胞、活化记忆CD4 + T细胞和M1巨噬细胞浸润较高。通路富集分析结果表明，TCR共表达特征高的患者具有显著激活的信号通路，如淋巴细胞增殖和激活、趋化因子结合和炎性细胞因子产生。此外，我们发现TCR共表达特征高的患者T细胞炎症基因表达谱（GEP）升高。：我们表明，TCR共表达特征可能作为接受免疫治疗的NSCLC患者预后的新生物标志物有用，特征高表明治疗反应更好。此外，我们发现TCR共表达特征高的患者具有具有有益抗肿瘤特征的肿瘤免疫微环境。
