免疫疗法
黑色素瘤
免疫系统
肿瘤微环境
CD8型
癌症研究
免疫检查点
T细胞
细胞
医学
癌症免疫疗法
计算生物学
生物
免疫学
遗传学
作者
Yucheng Dong,Zhizhuo Chen,Fan Yang,Jun Wei,Jiuzuo Huang,Xiao Long
标识
DOI:10.1016/j.tranon.2024.101910
摘要
Immune checkpoint inhibitors (ICB) therapy have emerged as effective treatments for melanomas. However, the response of melanoma patients to ICB has been highly heterogenous. Here, by analyzing integrated scRNA-seq datasets from melanoma patients, we revealed significant differences in the TiME composition between ICB-resistant and responsive tissues, with resistant or responsive tissues characterized by an abundance of myeloid cells and CD8+ T cells or CD4+ T cell predominance, respectively. Among CD4+ T cells, CD4+ CXCL13+ Tfh-like cells were associated with an immunosuppressive phenotype linked to immune escape-related genes and negative regulation of T cell activation. We also develop an immunotherapy response prediction model based on the composition of the immune compartment. Our predictive model was validated using CIBERSORTx on bulk RNA-seq datasets from melanoma patients pre- and post-ICB treatment and showed a better performance than other existing models. Our study presents an effective immunotherapy response prediction model with potential for further translation, as well as underscores the critical role of the TiME in influencing the response of melanomas to immunotherapy.
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