Distinct predictive biomarker candidates for response to anti-CTLA-4 and anti-PD-1 immunotherapy in melanoma patients.
Distinct predictive biomarker candidates for response to anti-CTLA-4 and anti-PD-1 immunotherapy in melanoma patients.
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DOI：
10.1186/s40425-018-0328-8
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发表时间：
2018-03-06
影响因子：
10.9
通讯作者：
Hodi FS
中科院分区：
文献类型：
--
作者：
Subrahmanyam PB;Dong Z;Gusenleitner D;Giobbie-Hurder A;Severgnini M;Zhou J;Manos M;Eastman LM;Maecker HT;Hodi FS
虽然免疫检查点封锁极大地改善了黑色素瘤等疾病的临床结果，但仍然需要预测性生物标志物来确定谁可能从哪种治疗中受益最多。迄今为止，大多数反应生物标志物已在肿瘤本身中得到鉴定。由于易于获取和采样的可重复性，可以从外周血中评估的生物标志物将更加理想。我们使用质谱流式细胞仪 (CyTOF) 全面分析黑色素瘤患者的外周血，以找到抗 CTLA-4 或抗 PD-1 治疗反应的预测生物标志物。使用一组约 40 个表面和细胞内标记物，我们进行了深入的表型和功能免疫分析，以确定潜在的候选预测生物标记物。使用 CyTOF 对基线外周血样本进行免疫分析表明，抗 CTLA-4 和抗 PD-1 疗法具有不同的候选生物标志物组。 CD4+和CD8+记忆/非记忆细胞和其他记忆亚群的分布在抗CTLA-4治疗的应答者和非应答者之间是不同的。在抗 PD-1（但不是抗 CTLA-4）治疗的患者中，我们发现应答者和非应答者之间表达 CD69 和 MIP-1β 的 NK 细胞存在差异。最后，使用多变量分析来开发响应预测模型。我们的结果表明抗 CTLA-4 和抗 PD-1 具有不同的候选预测生物标志物。 CD4+ 和 CD8+ 记忆 T 细胞亚群在对抗 CTLA-4 的反应中发挥重要作用，并且是潜在的生物标志物候选者。对于抗 PD-1 治疗，NK 细胞亚群（但不是记忆 T 细胞亚群）与治疗的临床反应相关。这些功能活跃的 NK 细胞亚群可能在抗 PD-1 触发的抗肿瘤反应中发挥关键作用。本文的在线版本 (10.1186/s40425-018-0328-8) 包含补充材料，可供授权用户使用。
While immune checkpoint blockade has greatly improved clinical outcomes in diseases such as melanoma, there remains a need for predictive biomarkers to determine who will likely benefit most from which therapy. To date, most biomarkers of response have been identified in the tumors themselves. Biomarkers that could be assessed from peripheral blood would be even more desirable, because of ease of access and reproducibility of sampling. We used mass cytometry (CyTOF) to comprehensively profile peripheral blood of melanoma patients, in order to find predictive biomarkers of response to anti-CTLA-4 or anti-PD-1 therapy. Using a panel of ~ 40 surface and intracellular markers, we performed in-depth phenotypic and functional immune profiling to identify potential predictive biomarker candidates. Immune profiling of baseline peripheral blood samples using CyTOF revealed that anti-CTLA-4 and anti-PD-1 therapies have distinct sets of candidate biomarkers. The distribution of CD4+ and CD8+ memory/non-memory cells and other memory subsets was different between responders and non-responders to anti-CTLA-4 therapy. In anti-PD-1 (but not anti-CTLA-4) treated patients, we discovered differences in CD69 and MIP-1β expressing NK cells between responders and non-responders. Finally, multivariate analysis was used to develop a model for the prediction of response. Our results indicate that anti-CTLA-4 and anti-PD-1 have distinct predictive biomarker candidates. CD4+ and CD8+ memory T cell subsets play an important role in response to anti-CTLA-4, and are potential biomarker candidates. For anti-PD-1 therapy, NK cell subsets (but not memory T cell subsets) correlated with clinical response to therapy. These functionally active NK cell subsets likely play a critical role in the anti-tumor response triggered by anti-PD-1. The online version of this article (10.1186/s40425-018-0328-8) contains supplementary material, which is available to authorized users.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
10.1
作者：
Hodi FS;Lawrence D;Lezcano C;Wu X;Zhou J;Sasada T;Zeng W;Giobbie-Hurder A;Atkins MB;Ibrahim N;Friedlander P;Flaherty KT;Murphy GF;Rodig S;Velazquez EF;Mihm MC Jr;Russell S;DiPiro PJ;Yap JT;Ramaiya N;Van den Abbeele AD;Gargano M;McDermott D
通讯作者：
McDermott D
影响因子：
30.5
作者：
Latchman, Y;Wood, CR;Freeman, GJ
通讯作者：
Freeman, GJ
DOI：
10.1158/1078-0432.ccr-15-2412
发表时间：
2016-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Martens A;Wistuba-Hamprecht K;Geukes Foppen M;Yuan J;Postow MA;Wong P;Romano E;Khammari A;Dreno B;Capone M;Ascierto PA;Di Giacomo AM;Maio M;Schilling B;Sucker A;Schadendorf D;Hassel JC;Eigentler TK;Martus P;Wolchok JD;Blank C;Pawelec G;Garbe C;Weide B
通讯作者：
Weide B