Immune regulatory genes impact the hot/cold tumor microenvironment, affecting cancer treatment and patient outcomes

作者：Mengmeng Sang, Jia Ge, Juan Ge, Gu Tang, Qiwen Wang, Jiarun Wu, Liming Mao, Xiaoling Ding, Xiaorong Zhou · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2024.1382842 · 被引用次数：13 · 研究领域：Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis、Pancreatic and Hepatic Oncology Research

Background and aims Immunologically hot tumors, characterized by an inflamed tumor microenvironment (TME), contrast significantly with immunologically cold tumors. The identification of these tumor immune subtypes holds clinical significance, as hot tumors may exhibit improved prognoses and heightened responsiveness to checkpoint blockade therapy. Nevertheless, as yet there is no consensus regarding the clinically relevant definition of hot/cold tumors, and the influence of immune genes on the formation of hot/cold tumors remains poorly understood. Methods Data for 33 different types of cancer were obtained from The Cancer Genome Atlas database, and their immune composition was assessed using the CIBERSORT algorithm. Tumors were categorized as either hot or cold based on their distinct immune composition, ongoing immune response, and overall survival. A customized immunogram was created to identify important immunological characteristics. Kyoto Encyclopedia of Genes and Genomes and Hallmark pathway enrichment were evaluated through gene set variation analysis. Additionally, hub genes that regulate the tumor microenvironment were identified, and their expression patterns were analyzed using single-cell RNA sequencing. Furthermore, drug sensitivity and molecular docking analyses were performed to identify potential drug candidates capable of transforming cold tumors into hot tumors. For validation, a clinical cohort of patients diagnosed with pancreatic adenocarcinoma was exami...