The tumor immune microenvironment transcriptomic subtypes of colorectal cancer for prognosis and development of precise immunotherapy.
The tumor immune microenvironment transcriptomic subtypes of colorectal cancer for prognosis and development of precise immunotherapy.
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结直肠癌肿瘤免疫微环境转录组亚型的预后和精确免疫治疗的发展。
DOI：
10.1093/gastro/goaa045
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发表时间：
2020-10
影响因子：
3.6
通讯作者：
Huang J
中科院分区：
文献类型：
--
作者：
Tang YQ;Chen TF;Zhang Y;Zhao XC;Zhang YZ;Wang GQ;Huang ML;Cai SL;Zhao J;Wei B;Huang J
Biomarkers based on immune context may guide prognosis prediction. T-cell inactivation, exclusion, or dysfunction could cause unfavorable tumor microenvironments, which affect immunotherapy and prognosis. However, none of the immuno-biomarkers reported to date can differentiate colorectal-cancer (CRC) patients. Thus, we aimed to classify CRC patients according to the levels of T-cell activation, exclusion, and dysfunction in the tumor microenvironment. RNAseq data of 618 CRC patients from The Cancer Genome Atlas and microarray data of 316 CRC patients from Gene Expression Omnibus were analysed using the Tumor Immune Dysfunction and Exclusion algorithm. Unsupervised clustering was used to classify patients. Based on the expression signatures of myeloid-derived suppressor cells, cancer-associated fibroblasts, M2-like tumor-associated macrophages, cytotoxic T-lymphocytes, and PD-L1, all patients were clustered into four subtypes: cluster 1 had a high level of immune dysfunction, cluster 2 had a low level of immune activation, cluster 3 had intense immune exclusion, and cluster 4 had a high level of immune activation and a moderate level of both dysfunction and exclusion signatures. Compared with cluster 1, the hazard ratios and 95% confidential intervals for overall survival were 0.63 (0.35–1.13) for cluster 2, 0.55 (0.29–1.03) for cluster 3, and 0.30 (0.14–0.64) for cluster 4 in multivariate Cox regression. Similar immune clustering and prognosis patterns were obtained upon validation in the GSE39582 cohort. In subgroup analysis, immune clustering was significantly associated with overall survival among stage I/II patients, microsatellite stable/instability-low patients, and patients not treated with adjuvant therapy. Our findings demonstrated that classifying CRC patients into different immune subtypes serves as a reliable prognosis predictor and may help to refine patient selection for personalized cancer immunotherapy.
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T细胞共刺激和共抑制的分子机制。
DOI：
10.1038/nri3405
发表时间：
2013-04
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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影响因子：
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作者：
Bacher JW;Flanagan LA;Smalley RL;Nassif NA;Burgart LJ;Halberg RB;Megid WM;Thibodeau SN
通讯作者：
Thibodeau SN
影响因子：
5.8
作者：
Hubbell, E;Liu, WM;Mei, R
通讯作者：
Mei, R
影响因子：
11.5
作者：
Torres, Sofia;Bartolome, Ruben A.;Ignacio Casal, J.
通讯作者：
Ignacio Casal, J.
结直肠癌的免疫基因组分层：对靶向免疫疗法发展的影响。
影响因子：
7.2
作者：
Lal N;Beggs AD;Willcox BE;Middleton GW
通讯作者：
Middleton GW