Linsley Peter S, Chaussabel Damien, Speake Cate
Department of Systems Immunology, Benaroya Research Institute, 1201 Ninth Avenue, Seattle, WA 98101-2795, United States of America.
PLoS One. 2015 Sep 23;10(9):e0138726. doi: 10.1371/journal.pone.0138726. eCollection 2015.
Enhancing pre-existing anti-tumor immunity leads to therapeutic benefit for some patients, but why some tumors are more immunogenic than others remains unresolved. We took a unique systems approach to relate patient survival to immune gene expression in >3,500 tumor RNAseq profiles from a dozen tumor types. We found significant links between immune gene expression and patient survival in 8/12 tumor types, with tumors partitioned by gene expression comprising distinct molecular subtypes. T/NK cell genes were most clearly survival-related for melanoma, head and neck, and bladder tumors, whereas myeloid cell genes were most clearly survival-related with kidney and breast tumors. T/NK or myeloid cell gene expression was linked to poor prognosis in bladder and kidney tumors, respectively, suggesting tumor-specific immunosuppressive checkpoints. Our results suggest new biomarkers for existing cancer immunotherapies and identify targets for new immunotherapies.
增强已有的抗肿瘤免疫力能使一些患者受益,但为何某些肿瘤比其他肿瘤具有更强的免疫原性仍未得到解决。我们采用了一种独特的系统方法,将患者生存率与来自十几种肿瘤类型的3500多个肿瘤RNA测序图谱中的免疫基因表达联系起来。我们发现,在12种肿瘤类型中的8种里,免疫基因表达与患者生存率之间存在显著关联,通过基因表达划分的肿瘤包含不同的分子亚型。对于黑色素瘤、头颈癌和膀胱癌,T/NK细胞基因与生存率的关系最为明显,而对于肾癌和乳腺癌,髓系细胞基因与生存率的关系最为明显。T/NK或髓系细胞基因表达分别与膀胱癌和肾癌的不良预后相关,提示存在肿瘤特异性免疫抑制检查点。我们的研究结果为现有的癌症免疫疗法提出了新的生物标志物,并确定了新免疫疗法的靶点。