Journal for immunotherapy of cancer · 2026
TCASIA: an integrative atlas linking alternative splicing landscapes for cancer immunotherapy.
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Zhang Yihao, Guo Yunzhi, Wang Haitao, Xiong Yi, Chen Minjun, Cai Ying, Li Xin, Wu Jun, Hao Jiaqi, Jin Su-Han, Zhang Wei, Dai Luohuan, Liu Hongwei, Li Jianfeng, Zhang Jiahui, Hecht Markus, Frey Benjamin, Gaipl Udo S, Chen Xin, Li Xuejun, Wang Shixiang, Ma Hu, Zhou Jian-Guo
Аннотация
BACKGROUND: Identifying robust predictive biomarkers for immune checkpoint blockade (ICB) remains a challenge. While alternative splicing (AS) shapes tumor immunity, the lack of large-scale, consensus-based datasets constrains the characterization of ICB-specific splicing landscapes.
METHODS: We developed TCASIA (the Cancer Alternative Splicing Immunotherapy Atlas), harmonizing >4000 samples across 29 cohorts. A rigorous "2-out-of-4" multi-algorithm consensus framework (rMATS, MAJIQ, SUPPA2, and SplAdder) with a fuzzy matching strategy was used to establish a high-confidence AS landscape.
RESULTS: TCASIA provides a robust toolkit linking splicing perturbations with clinical phenotypes (response, survival, and immune infiltration). Using this platform, we recapitulated the established FAS exon 6 skipping mechanism and identified IL7R exon 6 skipping as a functionally supported candidate associated with reduced CD8+ T-cell infiltration and poor survival in melanoma.
CONCLUSIONS: TCASIA provides an analytical atlas for investigating splicing-mediated immune evasion and prioritizing isoform-specific candidates for further functional and clinical validation in the context of ICB treatment.
METHODS: We developed TCASIA (the Cancer Alternative Splicing Immunotherapy Atlas), harmonizing >4000 samples across 29 cohorts. A rigorous "2-out-of-4" multi-algorithm consensus framework (rMATS, MAJIQ, SUPPA2, and SplAdder) with a fuzzy matching strategy was used to establish a high-confidence AS landscape.
RESULTS: TCASIA provides a robust toolkit linking splicing perturbations with clinical phenotypes (response, survival, and immune infiltration). Using this platform, we recapitulated the established FAS exon 6 skipping mechanism and identified IL7R exon 6 skipping as a functionally supported candidate associated with reduced CD8+ T-cell infiltration and poor survival in melanoma.
CONCLUSIONS: TCASIA provides an analytical atlas for investigating splicing-mediated immune evasion and prioritizing isoform-specific candidates for further functional and clinical validation in the context of ICB treatment.