Predictors of responses to immune checkpoint blockade in advanced melanoma.
Predictors of responses to immune checkpoint blockade in advanced melanoma.
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DOI：
10.1038/s41467-017-00608-2
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发表时间：
2017-09-19
影响因子：
16.6
通讯作者：
Zitvogel L
中科院分区：
文献类型：
--
作者：
Jacquelot N;Roberti MP;Enot DP;Rusakiewicz S;Ternès N;Jegou S;Woods DM;Sodré AL;Hansen M;Meirow Y;Sade-Feldman M;Burra A;Kwek SS;Flament C;Messaoudene M;Duong CPM;Chen L;Kwon BS;Anderson AC;Kuchroo VK;Weide B;Aubin F;Borg C;Dalle S;Beatrix O;Ayyoub M;Balme B;Tomasic G;Di Giacomo AM;Maio M;Schadendorf D;Melero I;Dréno B;Khammari A;Dummer R;Levesque M;Koguchi Y;Fong L;Lotem M;Baniyash M;Schmidt H;Svane IM;Kroemer G;Marabelle A;Michiels S;Cavalcanti A;Smyth MJ;Weber JS;Eggermont AM;Zitvogel L
免疫检查点阻断剂（ICB）已成为抗转移性黑色素瘤（MMel）临床治疗的关键疗法。鉴于免疫相关不良事件的频率和 ICB 使用的增加，CTLA-4 和/或 PD-1 阻断反应的预测因子代表了未满足的临床需求。我们使用基于系统生物学的方法对 37 名 III 期 MMel 患者的 779 种配对血液和肿瘤标志物进行了评估，分析了血液免疫参数与体外暴露于 ICB 后肿瘤浸润细胞的功能性免疫反应性之间的关联。基于该测定，我们在纳入 190 名接受 ipilimumab 治疗的 MMel 患者的 8 个队列中回顾性观察到，外周 T 细胞上的 PD-L1 表达对总体生存期和无进展生存期具有预测作用。此外，循环 CD8+ T 细胞上可检测到的 CD137 与接受 Ipilimumab++nivolumab（但不单独使用 nivolumab）辅助治疗后切除的 III 期 MMel 患者的无病状态相关。这些生物标志物应在 MMel 前瞻性试验中得到验证。转移性黑色素瘤的临床治疗需要检查点封锁反应的预测因子。在这里，作者使用免疫学测定来识别来自 III 期黑色素瘤切除患者的循环血细胞和肿瘤浸润淋巴细胞中的潜在预后/预测生物标志物。
Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we retrospectively observed, in eight cohorts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells was prognostic on overall and progression-free survival. Moreover, detectable CD137 on circulating CD8+ T cells was associated with the disease-free status of resected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone). These biomarkers should be validated in prospective trials in MMel. The clinical management of metastatic melanoma requires predictors of the response to checkpoint blockade. Here, the authors use immunological assays to identify potential prognostic/predictive biomarkers in circulating blood cells and in tumor-infiltrating lymphocytes from patients with resected stage III melanoma.
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影响因子：
8.8
作者：
Holmgaard RB;Zamarin D;Li Y;Gasmi B;Munn DH;Allison JP;Merghoub T;Wolchok JD
通讯作者：
Wolchok JD
影响因子：
64.5
作者：
Benci JL;Xu B;Qiu Y;Wu TJ;Dada H;Twyman-Saint Victor C;Cucolo L;Lee DSM;Pauken KE;Huang AC;Gangadhar TC;Amaravadi RK;Schuchter LM;Feldman MD;Ishwaran H;Vonderheide RH;Maity A;Wherry EJ;Minn AJ
通讯作者：
Minn AJ
影响因子：
7.4
作者：
Hamid O;Schmidt H;Nissan A;Ridolfi L;Aamdal S;Hansson J;Guida M;Hyams DM;Gómez H;Bastholt L;Chasalow SD;Berman D
通讯作者：
Berman D
影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.
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