The Identification of a Tumor Infiltration CD8+ T-Cell Gene Signature That Can Potentially Improve the Prognosis and Prediction of Immunization Responses in Papillary Renal Cell Carcinoma.
The Identification of a Tumor Infiltration CD8+ T-Cell Gene Signature That Can Potentially Improve the Prognosis and Prediction of Immunization Responses in Papillary Renal Cell Carcinoma.
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DOI：
10.3389/fonc.2021.757641
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发表时间：
2021
影响因子：
4.7
通讯作者：
Song J
中科院分区：
文献类型：
--
作者：
Wang J;Huang M;Huang P;Zhao J;Tan J;Huang F;Ma R;Xiao Y;Deng G;Wei L;Wei Q;Wang Z;He S;Shen J;Sooranna S;Meng L;Song J
CD 8 + T细胞是适应性免疫的重要效应细胞，与肿瘤细胞的免疫应答密切相关。了解肿瘤浸润CD 8 + T细胞在乳头状肾细胞癌（papillary renal cell carcinoma，papRCC）中的作用对于评估该疾病的预后过程和免疫治疗反应至关重要。利用papRCC的单细胞转录组数据筛选CD 8 + T细胞相关的差异表达基因，以实现以下研究。在此基础上，构建了与肿瘤浸润CD 8 + T细胞相关的预后基因签名，并使用癌症基因组图谱数据集进行了验证。确定papRCC病例的风险评分，并将其分类为高风险组或低风险组。采用多因素考克斯分析法和Kaplan-Meier生存曲线评估危险评分的预后意义。此外，还进一步探讨了病例遗传图谱评估免疫治疗反应的可能能力。使用单细胞RNA测序筛选了621个细胞死亡抑制RNA基因。然后鉴定了由7个基因（LYAR、YBX 1、PNRC 1、TCF 25、MYL 12 B、MINOS 1和LINC 01420）组成的基因签名，并且认为这一集合是一个独立的预后指标，可以有力地评估papRCC的总生存率。此外，数据允许papRCC病例落入高风险和低风险队列，表现出广泛的临床相关特征以及不同的CD 8 + T细胞免疫浸润和免疫治疗反应。我们的工作提供了一个可能的解释，目前的免疫检查点抑制元素打击papRCC的有限反应。此外，研究人员建立了一种新的基因签名，能够评估病例的预后和免疫反应。这也可能被认为是一个有前途的治疗目标的疾病。
CD8+ T cells, vital effectors pertaining to adaptive immunity, display close relationships to the immunization responses to kill tumor cells. Understanding the effect exerted by tumor infiltration CD8+ T cells in papillary renal cell carcinoma (papRCC) is critical for assessing the prognosis process and responses to immunization therapy in cases with this disease. The single-cell transcriptome data of papRCC were used for screening CD8+ T-cell-correlated differentially expressed genes to achieve the following investigations. On that basis, a prognosis gene signature associated with tumor infiltration CD8+ T cell was built and verified with The Cancer Genome Atlas data set. Risk scores were determined for papRCC cases and categorized as high- or low-risk groups. The prognosis significance for risk scores was assessed with multiple-variate Cox investigation and Kaplan–Meier survival curves. In addition, the possible capability exhibited by the genetic profiles of cases to assess the response to immunization therapy was further explored. Six hundred twenty-one cell death-inhibiting RNA genes were screened using single-cell RNA sequencing. A gene signature consisting of seven genes (LYAR, YBX1, PNRC1, TCF25, MYL12B, MINOS1, and LINC01420) was then identified, and this collective was considered to be an independent prognosis indicator that could strongly assess overall survival in papRCC. In addition, the data allowed papRCC cases to fall to cohorts at high and low risks, exhibiting a wide range of clinically related features as well as different CD8+ T-cell immunization infiltration and immunization therapy responses. Our work provides a possible explanation for the limited response of current immunization checkpoint-inhibiting elements for combating papRCC. Furthermore, the researchers built a novel genetic signature that was able to assess the prognosis and immunotherapeutic response of cases. This may also be considered as a promising therapeutic target for the disease.
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影响因子：
1.3
作者：
Therneau, TM;Li, HZ
通讯作者：
Li, HZ
影响因子：
6.4
作者：
Eich, Marie-Lisa;Chaux, Alcides;Netto, George J.
通讯作者：
Netto, George J.
影响因子：
15.9
作者：
Baitsch, Lukas;Baumgaertner, Petra;Speiser, Daniel E.
通讯作者：
Speiser, Daniel E.
DOI：
10.1056/nejmoa1510665
发表时间：
2015-11-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Motzer RJ;Escudier B;McDermott DF;George S;Hammers HJ;Srinivas S;Tykodi SS;Sosman JA;Procopio G;Plimack ER;Castellano D;Choueiri TK;Gurney H;Donskov F;Bono P;Wagstaff J;Gauler TC;Ueda T;Tomita Y;Schutz FA;Kollmannsberger C;Larkin J;Ravaud A;Simon JS;Xu LA;Waxman IM;Sharma P;CheckMate 025 Investigators
通讯作者：
CheckMate 025 Investigators
影响因子：
5.8
作者：
Ye M;Zhang J;Wei M;Liu B;Dong K
通讯作者：
Dong K