Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures.
Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures.
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DOI：
10.1186/s13059-016-1092-z
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发表时间：
2016-11-17
期刊：
影响因子：
12.3
通讯作者：
Hakimi AA
中科院分区：
文献类型：
--
作者：
Şenbabaoğlu Y;Gejman RS;Winer AG;Liu M;Van Allen EM;de Velasco G;Miao D;Ostrovnaya I;Drill E;Luna A;Weinhold N;Lee W;Manley BJ;Khalil DN;Kaffenberger SD;Chen Y;Danilova L;Voss MH;Coleman JA;Russo P;Reuter VE;Chan TA;Cheng EH;Scheinberg DA;Li MO;Choueiri TK;Hsieh JJ;Sander C;Hakimi AA
肿瘤浸润性免疫细胞与预后和对免疫疗法的反应有关;然而，不同免疫细胞亚群的水平和将它们吸引到肿瘤中的信号，例如抗原呈递机制基因的表达，仍然缺乏特征。在这里，我们采用基于基因表达的计算方法来分析19种癌症类型中24种免疫细胞群体的浸润水平。我们使用免疫浸润评分和T细胞浸润评分比较癌症类型，发现透明细胞肾细胞癌（ccRCC）是两种评分中最高的。使用免疫浸润概况以及转录组学和蛋白质组学数据集，我们表征了三组ccRCC肿瘤：T细胞富集、异质浸润和非浸润。我们观察到ccRCC肿瘤的免疫原性不能用突变负荷或新抗原负荷来解释，但与MHC I类抗原呈递机制表达（APM）高度相关。我们探讨了不同T细胞亚群的预后价值，并在两个队列中显示，Th 17细胞和CD 8 + T/Treg比值与改善的生存率相关，而Th 2细胞和T细胞亚群与阴性结局相关。对免疫浸润模式与肿瘤亚克隆结构之间关系的研究表明，APM和T细胞水平与亚克隆数呈负相关。我们的分析揭示了19种人类癌症的免疫浸润模式，并揭示了在ccRCC中具有预后效用和免疫生物标志物潜力的mRNA特征。本文的在线版本（doi：10.1186/s13059-016-1092-z）包含补充材料，可供授权用户使用。
Tumor-infiltrating immune cells have been linked to prognosis and response to immunotherapy; however, the levels of distinct immune cell subsets and the signals that draw them into a tumor, such as the expression of antigen presenting machinery genes, remain poorly characterized. Here, we employ a gene expression-based computational method to profile the infiltration levels of 24 immune cell populations in 19 cancer types. We compare cancer types using an immune infiltration score and a T cell infiltration score and find that clear cell renal cell carcinoma (ccRCC) is among the highest for both scores. Using immune infiltration profiles as well as transcriptomic and proteomic datasets, we characterize three groups of ccRCC tumors: T cell enriched, heterogeneously infiltrated, and non-infiltrated. We observe that the immunogenicity of ccRCC tumors cannot be explained by mutation load or neo-antigen load, but is highly correlated with MHC class I antigen presenting machinery expression (APM). We explore the prognostic value of distinct T cell subsets and show in two cohorts that Th17 cells and CD8+ T/Treg ratio are associated with improved survival, whereas Th2 cells and Tregs are associated with negative outcomes. Investigation of the association of immune infiltration patterns with the subclonal architecture of tumors shows that both APM and T cell levels are negatively associated with subclone number. Our analysis sheds light on the immune infiltration patterns of 19 human cancers and unravels mRNA signatures with prognostic utility and immunotherapeutic biomarker potential in ccRCC. The online version of this article (doi:10.1186/s13059-016-1092-z) contains supplementary material, which is available to authorized users.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
9.8
作者：
Elmasri, Harun;Ghelfi, Elisa;Yu, Chen-wei;Traphagen, Samantha;Cernadas, Manuela;Cao, Haiming;Shi, Guo-Ping;Plutzky, Jorge;Sahin, Mustafa;Hotamisligil, Gokhan;Cataltepe, Sule
通讯作者：
Cataltepe, Sule
影响因子：
48
作者：
Engstrom, Par G.;Steijger, Tamara;Sipos, Botond;Grant, Gregory R.;Kahles, Andre;Raetsch, Gunnar;Goldman, Nick;Hubbard, Tim J.;Harrow, Jennifer;Guigo, Roderic;Bertone, Paul
通讯作者：
Bertone, Paul
影响因子：
64.8
作者：
DuPage, Michel;Mazumdar, Claire;Schmidt, Leah M.;Cheung, Ann F.;Jacks, Tyler
通讯作者：
Jacks, Tyler