Gao Ze, Tao Yiran, Lai Yiming, Wang Qiong, Li Zean, Peng Shirong, Chen Junxiu, Cai Wenli, Li Kaiwen, Huang Hai
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Front Bioeng Biotechnol. 2020 Aug 6;8:930. doi: 10.3389/fbioe.2020.00930. eCollection 2020.
Immune checkpoint inhibitors (ICIs) treatment is becoming a new hope for cancer treatment. However, most prostate cancer (PCa) patients do not benefit from it. In order to achieve the accuracy of ICIs treatment in PCa and reduce unnecessary costs for patients, we have analyzed the data from TCGA database to find a indicator that can assist the choice of treatment. By analyzing the data of PCa patients with TMB analysis and immune infiltration analysis, we found the expression of immune cells in different immune infiltration groups. Commonly used markers of ICIs, expressed on CD8 T cell, were highly expressed in the high immune group. Then we used the forimmune cytolytic activity (CYT) to determine its relationship with the target of ICIs treatment. Through the analysis of CYT score and the ligands of immune checkpoints, we found that there was a significant correlation between them. With the increase of CYT score, the expression of CD80/86, PD-L1/L2, TNFSF14, and LGALS9 also increased gradually. Similarly, CD8 T cells were significantly increased in the CYT high group compared with the CYT low group in PRAD. The present research provides novel insights into the immune microenvironment of PRAD and potential immunotherapies. The proposed CYT score is a clinically promising indicator that can serve as a marker to assist anti-PD-L1 or other ICIs treatment. At the same time, it also provides a basis for the selection of other immune checkpoint drugs.
免疫检查点抑制剂（ICIs）治疗正成为癌症治疗的新希望。然而，大多数前列腺癌（PCa）患者并未从中获益。为了实现PCa中ICIs治疗的准确性并降低患者的不必要费用，我们分析了TCGA数据库中的数据以找到一个能够辅助治疗选择的指标。通过对PCa患者进行肿瘤突变负荷（TMB）分析和免疫浸润分析，我们发现了不同免疫浸润组中免疫细胞的表达情况。ICIs常用的标志物在CD8 T细胞上表达，在高免疫组中高表达。然后我们使用免疫细胞溶解活性（CYT）来确定其与ICIs治疗靶点的关系。通过分析CYT评分和免疫检查点的配体，我们发现它们之间存在显著相关性。随着CYT评分的增加，CD80/86、PD-L1/L2、TNFSF14和LGALS9的表达也逐渐增加。同样，在前列腺腺癌（PRAD）中，CYT高分组的CD8 T细胞与CYT低分组相比显著增加。本研究为PRAD的免疫微环境和潜在免疫治疗提供了新的见解。所提出的CYT评分是一个具有临床前景的指标，可作为辅助抗PD-L1或其他ICIs治疗的标志物。同时，它也为其他免疫检查点药物的选择提供了依据。
