Wang Jie, Huang Meiying, Huang Peng, Zhao Jingjie, Tan Junhua, Huang Feifan, Ma Ruiying, Xiao Yu, Deng Gao, Wei Liuzhi, Wei Qiuju, Wang Zechen, He Siyuan, Shen Jiajia, Sooranna Suren, Meng Lingzhang, Song Jian
Center for Systemic Inflammation Research (CSIR), School of Preclinical Medicine, Youjiang Medical University for Nationalities, Baise, China.
Department of Renal Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
Front Oncol. 2021 Nov 10;11:757641. doi: 10.3389/fonc.2021.757641. eCollection 2021.
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 (, , , , , , and ) 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.
CD8+ T细胞是适应性免疫的重要效应细胞,与杀伤肿瘤细胞的免疫反应密切相关。了解肿瘤浸润性CD8+ T细胞在乳头状肾细胞癌(papRCC)中所发挥的作用,对于评估该疾病患者的预后过程及免疫治疗反应至关重要。
利用papRCC的单细胞转录组数据筛选与CD8+ T细胞相关的差异表达基因,以进行以下研究。在此基础上,构建与肿瘤浸润性CD8+ T细胞相关的预后基因特征,并使用癌症基因组图谱数据集进行验证。确定papRCC病例的风险评分,并将其分为高风险或低风险组。通过多变量Cox研究和Kaplan-Meier生存曲线评估风险评分的预后意义。此外,进一步探索病例基因谱评估免疫治疗反应的潜在能力。
通过单细胞RNA测序筛选出621个抑制细胞死亡的RNA基因。随后鉴定出一个由7个基因(、、、、、和)组成的基因特征,该组合被认为是一个独立的预后指标,能够有力地评估papRCC的总生存期。此外,这些数据使papRCC病例分为高风险和低风险队列,呈现出广泛的临床相关特征以及不同的CD8+ T细胞免疫浸润和免疫治疗反应。
我们的工作为当前免疫检查点抑制元件对抗papRCC反应有限提供了一种可能的解释。此外,研究人员构建了一种新型基因特征,能够评估病例的预后和免疫治疗反应。这也可能被视为该疾病有前景的治疗靶点。