A peripheral immune signature of responsiveness to PD-1 blockade in patients with classical Hodgkin lymphoma.
A peripheral immune signature of responsiveness to PD-1 blockade in patients with classical Hodgkin lymphoma.
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DOI：
10.1038/s41591-020-1006-1
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发表时间：
2020-09
期刊：
影响因子：
82.9
通讯作者：
Shipp, Margaret A.
中科院分区：
文献类型：
--
作者：
Cader, Fathima Zumla;Hu, Xihao;Goh, Walter L.;Wienand, Kirsty;Ouyang, Jing;Mandato, Elisa;Redd, Robert;Lawton, Lee N.;Chen, Pei-Hsuan;Weirather, Jason L.;Schackmann, Ron C. J.;Li, Bo;Ma, Wenjiang;Armand, Philippe;Rodig, Scott J.;Neuberg, Donna;Liu, X. Shirley;Shipp, Margaret A.
PD-1阻断在典型霍奇金淋巴瘤（cHL）中非常有效，这些淋巴瘤表现出频繁的染色体9p24.1/CD 274（PD-L1）/PDC 1 LG 2（PD-L2）拷贝增加。然而，在这种主要为MHC I类阴性的肿瘤中，抗PD-1治疗的作用机制仍不明确。我们利用T细胞受体（TCR）测序和飞行时间分析（CyTOF）细胞计数的互补方法，在CheckMate 205 II期临床试验（NCT 02181738）中治疗的56例患者中获得对PD-1阻断反应性的外周免疫特征。抗PD-1治疗在具有不同基线TCR库和治疗期间单克隆相关扩增的患者中最有效。在治疗过程中，CD 4+而非CD 8 + TCR多样性显著增加，在获得完全缓解的患者中最显著。此外，应答患者的活化NK细胞丰度增加，新鉴定出CD 3 − CD 68 + CD 4 +GrB+亚群。这些研究强调了最近扩增的克隆多样性CD 4 + T细胞和先天效应物在cHL中PD-1阻断的功效中的作用。
PD-1 blockade is highly effective in classical Hodgkin lymphomas (cHLs) which exhibit frequent chromosome 9p24.1/CD274 (PD-L1)/PDC1LG2 (PD-L2) copy gains. However, in this largely MHC class I-negative tumor, the mechanism of action of anti-PD-1 therapy remains undefined. We utilized the complementary approaches of T-cell receptor (TCR) sequencing and cytometry by time-of-flight analysis (CyTOF) to obtain a peripheral immune signature of responsiveness to PD-1 blockade in 56 patients treated in the CheckMate 205 phase II clinical trial (NCT02181738). Anti PD-1 therapy was most effective in patients with a diverse baseline TCR repertoire and an associated expansion of singleton clones during treatment. CD4+, but not CD8+, TCR diversity significantly increased during therapy, most strikingly in patients who achieved complete responses. Additionally, responding patients had an increased abundance of activated NK cells and a newly identified CD3−CD68+CD4+GrB+ subset. These studies highlight the roles of recently expanded, clonally diverse CD4+ T cells and innate effectors in the efficacy of PD-1 blockade in cHL.
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DOI：
10.1084/jem.20160801
发表时间：
2017-04-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Juneja VR;McGuire KA;Manguso RT;LaFleur MW;Collins N;Haining WN;Freeman GJ;Sharpe AH
通讯作者：
Sharpe AH
影响因子：
64.8
作者：
Im SJ;Hashimoto M;Gerner MY;Lee J;Kissick HT;Burger MC;Shan Q;Hale JS;Lee J;Nasti TH;Sharpe AH;Freeman GJ;Germain RN;Nakaya HI;Xue HH;Ahmed R
通讯作者：
Ahmed R
影响因子：
20.3
作者：
Green, Michael R.;Monti, Stefano;Shipp, Margaret A.
通讯作者：
Shipp, Margaret A.
影响因子：
20.3
作者：
Cader, Fathima Zumla;Schackmann, Ron C. J.;Shipp, Margaret A.
通讯作者：
Shipp, Margaret A.
影响因子：
16.6
作者：
Johnson DB;Estrada MV;Salgado R;Sanchez V;Doxie DB;Opalenik SR;Vilgelm AE;Feld E;Johnson AS;Greenplate AR;Sanders ME;Lovly CM;Frederick DT;Kelley MC;Richmond A;Irish JM;Shyr Y;Sullivan RJ;Puzanov I;Sosman JA;Balko JM
通讯作者：
Balko JM