Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong-An Road, Shanghai 200032, PR China; The Genius Medicine Consortium (TGMC), PR China.
Medical College of Soochow University, Suzhou, Jiangsu 215000, PR China; The Genius Medicine Consortium (TGMC), PR China.
Int Immunopharmacol. 2020 Aug;85:106633. doi: 10.1016/j.intimp.2020.106633. Epub 2020 Jun 5.
Immunotherapy has recently become a powerful weapon against cancer. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) was the first immune checkpoint used for immunotherapy. However, CTLA-4-related mechanisms in various cancers have not been comprehensively investigated. This aim of this study was an in-depth investigation of CTLA-4 in the tumor microenvironment and its relationship with other immunomodulators, immune-related pathways and survival outcomes of 33 cancer types. Overall 9,743 tumor samples and 710 normal samples of 33 cancer types from The Cancer Genome Atlas (TCGA) database were included. CTLA-4 expression level was compared between tumor and normal tissues in 22 cancer types. The microenvironment cell populations (MCP)-counter method was used to analyze the correlation between CTLA-4 and immune cell infiltration. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to investigate its relationship with immune pathways. Survival analysis was conducted using the Kaplan-Meier method with log-rank test. CTLA-4 expression was found to be increased in some types of cancer and decreased in other cancer types (P < 0.05). When comparing between different tumor tissues, CTLA-4 was lowest in uveal melanoma (UVM). MCP analysis demonstrated that CTLA-4 had a strong correlation with T cells in almost all cancer types and that CTLA-4 showed a positive correlation with most immune cells in UVM. Immune pathway analysis found that CTLA-4 is involved in a variety of immune pathways. Survival analysis revealed that CTLA-4 can predict patients' survival outcomes. This comprehensive analysis of CTLA-4 will promote anti-CTLA-4 therapy and personalized combined immunotherapy.
免疫疗法最近已成为对抗癌症的有力武器。细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）是第一种用于免疫疗法的免疫检查点。然而，各种癌症中 CTLA-4 相关机制尚未得到全面研究。本研究旨在深入研究 CTLA-4 在肿瘤微环境中的作用及其与其他免疫调节剂、免疫相关通路和 33 种癌症类型的生存结局的关系。共纳入 33 种癌症类型的 TCGA 数据库中的 9743 个肿瘤样本和 710 个正常样本。在 22 种癌症类型中比较了肿瘤组织和正常组织中 CTLA-4 的表达水平。采用 MCP-counter 方法分析 CTLA-4 与免疫细胞浸润的相关性。采用基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析方法研究其与免疫通路的关系。采用 Kaplan-Meier 方法和对数秩检验进行生存分析。结果发现，CTLA-4 在某些类型的癌症中表达增加，而在其他癌症类型中表达降低（P<0.05）。在比较不同肿瘤组织时，脉络膜黑色素瘤（UVM）中 CTLA-4 表达最低。MCP 分析表明，CTLA-4 在几乎所有癌症类型中与 T 细胞具有很强的相关性，并且在 UVM 中 CTLA-4 与大多数免疫细胞呈正相关。免疫通路分析发现 CTLA-4 参与多种免疫通路。生存分析表明 CTLA-4 可预测患者的生存结局。本研究对 CTLA-4 的全面分析将促进抗 CTLA-4 治疗和个性化联合免疫治疗。
