Comprehensive analyses of tumor immunity: implications for cancer immunotherapy.
Comprehensive analyses of tumor immunity: implications for cancer immunotherapy.
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DOI：
10.1186/s13059-016-1028-7
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发表时间：
2016-08-22
期刊：
影响因子：
12.3
通讯作者：
Liu XS
中科院分区：
文献类型：
--
作者：
Li B;Severson E;Pignon JC;Zhao H;Li T;Novak J;Jiang P;Shen H;Aster JC;Rodig S;Signoretti S;Liu JS;Liu XS
了解肿瘤与宿主免疫系统之间的相互作用对于发现预后生物标志物、减少耐药性和开发新疗法至关重要。需要新的计算方法来估计肿瘤浸润免疫细胞并了解癌症中的肿瘤免疫相互作用。我们分析了来自癌症基因组图谱（TCGA）的23种癌症类型的10，000多个RNA-seq样本中的肿瘤浸润免疫细胞。我们计算推断的免疫浸润与患者临床特征、病毒感染状态和癌症遗传改变的关联比其他计算方法更强。对癌症/睾丸抗原表达和CD 8 T细胞丰度的分析表明，MAGEA 3是黑色素瘤的潜在免疫靶点，但不是非小细胞肺癌的潜在免疫靶点，并暗示SPAG 5是多种癌症的替代癌症疫苗靶点。我们发现表达高水平CTLA 4的黑色素瘤在CD 8 T细胞浸润方面分为两个不同的组，这可能影响抗CTLA 4药物的临床反应。我们观察到类似的二分法TIM 3表达相对于CD 8 T细胞在肾癌和实验验证。丰富的免疫浸润，以及我们的下游分析和发现，可以通过TIMER访问，TIMER是一个公共资源，网址是http://cistrome.org/TIMER。我们开发了一种计算方法来研究肿瘤浸润免疫细胞及其与癌细胞的相互作用。我们的免疫浸润水平，临床关联以及预测的治疗标志物资源可以为有效的癌症疫苗和检查点阻断疗法提供信息。本文的在线版本（doi：10.1186/s13059-016-1028-7）包含补充材料，可供授权用户使用。
Understanding the interactions between tumor and the host immune system is critical to finding prognostic biomarkers, reducing drug resistance, and developing new therapies. Novel computational methods are needed to estimate tumor-infiltrating immune cells and understand tumor–immune interactions in cancers. We analyze tumor-infiltrating immune cells in over 10,000 RNA-seq samples across 23 cancer types from The Cancer Genome Atlas (TCGA). Our computationally inferred immune infiltrates associate much more strongly with patient clinical features, viral infection status, and cancer genetic alterations than other computational approaches. Analysis of cancer/testis antigen expression and CD8 T-cell abundance suggests that MAGEA3 is a potential immune target in melanoma, but not in non-small cell lung cancer, and implicates SPAG5 as an alternative cancer vaccine target in multiple cancers. We find that melanomas expressing high levels of CTLA4 separate into two distinct groups with respect to CD8 T-cell infiltration, which might influence clinical responses to anti-CTLA4 agents. We observe similar dichotomy of TIM3 expression with respect to CD8 T cells in kidney cancer and validate it experimentally. The abundance of immune infiltration, together with our downstream analyses and findings, are accessible through TIMER, a public resource at http://cistrome.org/TIMER. We develop a computational approach to study tumor-infiltrating immune cells and their interactions with cancer cells. Our resource of immune-infiltrate levels, clinical associations, as well as predicted therapeutic markers may inform effective cancer vaccine and checkpoint blockade therapies. The online version of this article (doi:10.1186/s13059-016-1028-7) contains supplementary material, which is available to authorized users.