Pan-cancer adaptive immune resistance as defined by the Tumor Inflammation Signature (TIS): results from The Cancer Genome Atlas (TCGA).
Pan-cancer adaptive immune resistance as defined by the Tumor Inflammation Signature (TIS): results from The Cancer Genome Atlas (TCGA).
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DOI：
10.1186/s40425-018-0367-1
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发表时间：
2018-06-22
影响因子：
10.9
通讯作者：
Cesano A
中科院分区：
文献类型：
--
作者：
Danaher P;Warren S;Lu R;Samayoa J;Sullivan A;Pekker I;Wallden B;Marincola FM;Cesano A
肿瘤炎症信号（TIS）是一种仅用于研究的（IUO） 18基因信号，用于测量肿瘤中存在但抑制的适应性免疫反应。TIS已被证明对抗pd1药物派姆单抗有反应的患者具有丰富的疗效。为了探索肿瘤类型内部和跨类型的这种免疫表型，我们将TIS算法应用于从癌症基因组图谱（TCGA）下载的9000多个肿瘤基因表达谱。正如先前证据所预期的那样，已知对抗程序性细胞死亡蛋白1 （PD-1）阻断具有临床敏感性的肿瘤具有更高的平均TIS评分。此外，TIS评分在肿瘤类型内的差异大于肿瘤类型之间的差异，并且在每种肿瘤类型中，可以识别出评分较高的患者子集，尽管每种肿瘤类型的患病率不同，后者与观察到的抗PD-1阻断的临床反应性一致。值得注意的是，在大多数肿瘤中，TIS评分与突变负荷的相关性很小，根据TIS中位数评分对肿瘤进行排名与通过突变负荷对同一肿瘤进行排名相比，对PD-1/PD-1配体1 （PD-L1）阻断的临床敏感性存在差异。TIS算法基因的表达模式在不同的肿瘤类型中是保守的，但在大多数癌症中似乎对预后的影响最小，这与TIS评分作为炎症肿瘤表型的泛癌症测量相一致。对TIS的患病率和变异性进行表征将有助于增进对未经治疗肿瘤免疫状态的了解，并可能改善免疫治疗药物试验的适应症选择。本文的在线版本（10.1186/s40425-018-0367-1）包含补充材料，可供授权用户使用。
The Tumor Inflammation Signature (TIS) is an investigational use only (IUO) 18-gene signature that measures a pre-existing but suppressed adaptive immune response within tumors. The TIS has been shown to enrich for patients who respond to the anti-PD1 agent pembrolizumab. To explore this immune phenotype within and across tumor types, we applied the TIS algorithm to over 9000 tumor gene expression profiles downloaded from The Cancer Genome Atlas (TCGA). As expected based on prior evidence, tumors with known clinical sensitivity to anti-programmed cell death protein 1 (PD-1) blockade had higher average TIS scores. Furthermore, TIS scores were more variable within than between tumor types, and within each tumor type a subset of patients with elevated scores was identifiable although with different prevalence associated with each tumor type, the latter consistent with the observed clinical responsiveness to anti PD-1 blockade. Notably, TIS scores only minimally correlated with mutation load in most tumors and ranking tumors by median TIS score showed differing association to clinical sensitivity to PD-1/PD-1 ligand 1 (PD-L1) blockade than ranking of the same tumors by mutation load. The expression patterns of the TIS algorithm genes were conserved across tumor types yet appeared to be minimally prognostic in most cancers, consistent with the TIS score serving as a pan-cancer measurement of the inflamed tumor phenotype. Characterization of the prevalence and variability of TIS will lead to increased understanding of the immune status of untreated tumors and may lead to improved indication selection for testing immunotherapy agents. The online version of this article (10.1186/s40425-018-0367-1) contains supplementary material, which is available to authorized users.
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影响因子：
5.8
作者：
Diederichsen, ACP;Hjelmborg, JV;Fenger, C
通讯作者：
Fenger, C
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM
影响因子：
6
作者：
Coppola, Domenico;Nebozhyn, Michael;Mule, James J.
通讯作者：
Mule, James J.
影响因子：
3.8
作者：
Dirix LY;Takacs I;Jerusalem G;Nikolinakos P;Arkenau HT;Forero-Torres A;Boccia R;Lippman ME;Somer R;Smakal M;Emens LA;Hrinczenko B;Edenfield W;Gurtler J;von Heydebreck A;Grote HJ;Chin K;Hamilton EP
通讯作者：
Hamilton EP