CD4陽性T細胞活性化におけるトランスクリプトームワイドメンデルランダム化および単一細胞解析による大腸がんの免疫療法標的の解明

Immunotherapy has become a promising treatment for various cancers, including colorectal cancer (CRC). Despite significant progress, identifying immune cell-specific therapeutic targets remains challenging, especially for CD4⁺ T cells, whose activation influences both anti-tumor and pro-tumor immune responses. This study aims to identify potential immunotherapy targets for CRC by exploring the causal relationships between CD4⁺ T cell activation-associated genes and CRC through Mendelian randomization (MR) and single-cell RNA sequencing (scRNA-seq). We used transcriptome-wide MR, summary-based MR (SMR), and colocalization analysis, along with validation through multi-omics approaches, to identify 28 dynamic CD4⁺ T cell-related genes as therapeutic targets. Notably, PARP14 and ORMDL3 emerged as key targets, with strong associations to immune therapy resistance and CRC. This research highlights the critical role of CD4⁺ T cell activation in CRC progression and identifies novel potential targets for immunotherapy.