Department of Pediatric Surgery, The First Hospital of Jilin University, Changchun, China.
Department of Neonatology, The First Hospital of Jilin University, Changchun, China.
Front Immunol. 2021 Oct 18;12:713001. doi: 10.3389/fimmu.2021.713001. eCollection 2021.
has been reported to play dual roles in cancer; however, its effects on the tumor microenvironment (TME), immunotherapy, and prognosis in melanoma remain largely unclear. This study was aimed to uncover the effects of on TME, immunotherapy and prognosis in patients with melanoma.
RNA-seq data, drug sensitivity data, and clinical data were obtained from TCGA, GEO, CCLE, and CTRP. Log-rank test was used to determine the survival value of . Univariate and multivariate Cox regression analyses were employed to determine the independent predictors of survival outcomes. DAVID and GSEA were used to perform gene set functional annotations. ssGSEA was used to explore the association between and immune infiltrates. ConsensusClusterPlus was used to classify melanoma tissues into hot tumors or cold tumors.
Clinically, was negatively correlated with Breslow depth ( = 0.00042) and positively associated with response to radiotherapy ( = 0.038). High expression showed an improved survival outcome ( = 0.00016), and could serve as an independent predictor of survival outcomes (hazard ratio: 0.32 - 0.88, = 0.015). Functionally, elevated expression could induce an enhanced immune response and pyroptosis ( = 0.64, = 1.2e-55), autophagy ( = 0.37, = 7.1e-17) and apoptosis ( = 0.47, = 1.1e-27) in patients with melanoma. Mechanistically, elevated expression was positively correlated with cytotoxic cytokines (including and ), enhanced immune infiltrates, and elevated CD8/Treg ratio ( = 0.14, = 0.02), possibly driving CD8 T cell infiltration by suppressing β-catenin signaling in the TME. Furthermore, was significantly associated with hot tumor state, multiple predictors of response to immunotherapy, and improved drug response in patients with melanoma.
was correlated with enriched CD8 T cells, desirable therapeutic response and improved prognosis. It thus can be utilized as a promising modulator in the development of cytokine-based immunotherapy for melanoma.
已被报道在癌症中发挥双重作用；然而，其对黑色素瘤肿瘤微环境（TME）、免疫治疗和预后的影响在很大程度上仍不清楚。本研究旨在揭示在黑色素瘤患者中对 TME、免疫治疗和预后的影响。
从 TCGA、GEO、CCLE 和 CTRP 中获取 RNA-seq 数据、药物敏感性数据和临床数据。采用 Log-rank 检验确定的生存价值。采用单因素和多因素 Cox 回归分析确定生存结果的独立预测因子。采用 DAVID 和 GSEA 进行基因集功能注释。采用 ssGSEA 探索与免疫浸润的关联。采用 ConsensusClusterPlus 将黑色素瘤组织分类为热肿瘤或冷肿瘤。
临床分析表明，与 Breslow 深度呈负相关（=0.00042），与放射治疗反应呈正相关（=0.038）。高表达显示出改善的生存结果（=0.00016），并且可以作为生存结果的独立预测因子（风险比：0.32-0.88，=0.015）。功能上，升高的表达可以诱导黑色素瘤患者增强免疫反应和细胞焦亡（=0.64，=1.2e-55）、自噬（=0.37，=7.1e-17）和细胞凋亡（=0.47，=1.1e-27）。机制上，升高的表达与细胞毒性细胞因子（包括和）、增强的免疫浸润和升高的 CD8/Treg 比值呈正相关（=0.14，=0.02），可能通过抑制 TME 中的β-连环蛋白信号驱动 CD8 T 细胞浸润。此外，与热肿瘤状态、免疫治疗反应的多个预测因子以及黑色素瘤患者药物反应的改善显著相关。
与丰富的 CD8 T 细胞、理想的治疗反应和改善的预后相关。因此，它可以作为黑色素瘤细胞因子为基础的免疫治疗开发的有前途的调节剂。
