Combined tumor and immune signals from genomes or transcriptomes predict outcomes of checkpoint inhibition in melanoma.
Combined tumor and immune signals from genomes or transcriptomes predict outcomes of checkpoint inhibition in melanoma.
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DOI：
10.1016/j.xcrm.2021.100500
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发表时间：
2022-02-15
期刊：
影响因子：
--
通讯作者：
Hacohen N
中科院分区：
文献类型：
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作者：
Freeman SS;Sade-Feldman M;Kim J;Stewart C;Gonye ALK;Ravi A;Arniella MB;Gushterova I;LaSalle TJ;Blaum EM;Yizhak K;Frederick DT;Sharova T;Leshchiner I;Elagina L;Spiro OG;Livitz D;Rosebrock D;Aguet F;Carrot-Zhang J;Ha G;Lin Z;Chen JH;Barzily-Rokni M;Hammond MR;Vitzthum von Eckstaedt HC;Blackmon SM;Jiao YJ;Gabriel S;Lawrence DP;Duncan LM;Stemmer-Rachamimov AO;Wargo JA;Flaherty KT;Sullivan RJ;Boland GM;Meyerson M;Getz G;Hacohen N
免疫检查点阻断（CPB）改善了黑色素瘤的结局，但许多患者仍然没有反应。肿瘤突变负荷（TMB）和肿瘤浸润性T细胞与应答相关，综合模型可改善生存预测。然而，使用单一检测（DNA/RNA）的数据整合免疫/肿瘤固有特征仍然有待探索。在这里，我们分析了来自新的和已发表的189和178例接受CPB的黑色素瘤患者队列的肿瘤的全外显子组和批量RNA测序。使用DNA，我们从重排的TCR/IG序列计算T细胞和B细胞负荷（TCB/BCB），发现与其他患者相比，TMB高和TCB高或BCB高的患者具有改善的结局。通过结合免疫和肿瘤表达的基因对，我们确定了三个与反应和生存相关的基因对，这些基因对在独立的队列中得到了验证。顶部模型包括淋巴细胞表达的MAP 4K 1和肿瘤表达的TBX 3。总体而言，结合免疫和肿瘤测量的基于RNA或DNA的模型改善了对黑色素瘤CPB结果的预测。T和B细胞负荷（TCB/BCB）可以从重排的TCR/IG DNA序列计算。基于DNA的TCB或BCB与TMB测量的组合改善了结果预测。对接受检查点抑制剂治疗的黑色素瘤患者的DNA和RNA测序数据进行荟萃分析，以确定与结果相关的因素组合。使用来自DNA或RNA检测的数据，他们得出结论，结合肿瘤和免疫测量的模型可以改善免疫治疗结果的预测。
Immune checkpoint blockade (CPB) improves melanoma outcomes, but many patients still do not respond. Tumor mutational burden (TMB) and tumor-infiltrating T cells are associated with response, and integrative models improve survival prediction. However, integrating immune/tumor-intrinsic features using data from a single assay (DNA/RNA) remains underexplored. Here, we analyze whole-exome and bulk RNA sequencing of tumors from new and published cohorts of 189 and 178 patients with melanoma receiving CPB, respectively. Using DNA, we calculate T cell and B cell burdens (TCB/BCB) from rearranged TCR/Ig sequences and find that patients with TMBhigh and TCBhigh or BCBhigh have improved outcomes compared to other patients. By combining pairs of immune- and tumor-expressed genes, we identify three gene pairs associated with response and survival, which validate in independent cohorts. The top model includes lymphocyte-expressed MAP4K1 and tumor-expressed TBX3. Overall, RNA or DNA-based models combining immune and tumor measures improve predictions of melanoma CPB outcomes. T and B cell burden (TCB/BCB) can be calculated from rearranged TCR/Ig DNA sequences Combining DNA-based TCB or BCB with TMB measurements improves outcome prediction RNA subtypes reflect tumor differentiation or immune abundance and predict survival Gene-pair MAP4K1 and TBX3 expression predict outcome and validate in independent data Freeman et al. perform a meta-analysis of DNA and RNA-sequencing data from melanoma patients treated with checkpoint inhibitors to identify combinations of factors associated with outcome. Using data from either a DNA or RNA assay, they conclude that models incorporating tumor and immune measurements can improve predictions of immunotherapy outcomes.
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影响因子：
46.9
作者：
Bolotin DA;Poslavsky S;Davydov AN;Frenkel FE;Fanchi L;Zolotareva OI;Hemmers S;Putintseva EV;Obraztsova AS;Shugay M;Ataullakhanov RI;Rudensky AY;Schumacher TN;Chudakov DM
通讯作者：
Chudakov DM
影响因子：
28.2
作者：
Chen PL;Roh W;Reuben A;Cooper ZA;Spencer CN;Prieto PA;Miller JP;Bassett RL;Gopalakrishnan V;Wani K;De Macedo MP;Austin-Breneman JL;Jiang H;Chang Q;Reddy SM;Chen WS;Tetzlaff MT;Broaddus RJ;Davies MA;Gershenwald JE;Haydu L;Lazar AJ;Patel SP;Hwu P;Hwu WJ;Diab A;Glitza IC;Woodman SE;Vence LM;Wistuba II;Amaria RN;Kwong LN;Prieto V;Davis RE;Ma W;Overwijk WW;Sharpe AH;Hu J;Futreal PA;Blando J;Sharma P;Allison JP;Chin L;Wargo JA
通讯作者：
Wargo JA
影响因子：
64.8
作者：
Cabrita, Rita;Lauss, Martin;Jonsson, Goran
通讯作者：
Jonsson, Goran
影响因子：
82.9
作者：
Auslander N;Zhang G;Lee JS;Frederick DT;Miao B;Moll T;Tian T;Wei Z;Madan S;Sullivan RJ;Boland G;Flaherty K;Herlyn M;Ruppin E
通讯作者：
Ruppin E
影响因子：
14.9
作者：
Costello M;Pugh TJ;Fennell TJ;Stewart C;Lichtenstein L;Meldrim JC;Fostel JL;Friedrich DC;Perrin D;Dionne D;Kim S;Gabriel SB;Lander ES;Fisher S;Getz G
通讯作者：
Getz G