Tissue-resident memory and circulating T cells are early responders to pre-surgical cancer immunotherapy.
Tissue-resident memory and circulating T cells are early responders to pre-surgical cancer immunotherapy.
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组织驻留记忆T细胞和循环T细胞是术前癌症免疫疗法的早期应答细胞。
DOI：
10.1016/j.cell.2022.06.018
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发表时间：
2022-08-04
期刊：
影响因子：
64.5
通讯作者：
Wucherpfennig, Kai W.
中科院分区：
文献类型：
--
作者：
Luoma, Adrienne M.;Suo, Shengbao;Wang, Yifan;Gunasti, Lauren;Porter, Caroline B. M.;Nabilsi, Nancy;Tadros, Jenny;Ferretti, Andrew P.;Liao, Sida;Gurer, Cagan;Chen, Yu-Hui;Criscitiello, Shana;Ricker, Cora A.;Dionne, Danielle;Rozenblatt-Rosen, Orit;Uppaluri, Ravindra;Haddad, Robert I.;Ashenberg, Orr;Regev, Aviv;Van Allen, Eliezer M.;MacBeath, Gavin;Schoenfeld, Jonathan D.;Wucherpfennig, Kai W.
新佐剂免疫检查点阻断已显示出良好的临床活性。在这里，我们在一项临床试验(NCT02919683)中研究了接受新佐剂抗PD-1或抗PD-1/CTLA-4治疗的口腔癌患者肿瘤浸润性和循环免疫细胞的早期动力学。在免疫治疗期间克隆扩增的肿瘤浸润性CD8 T细胞表现出组织驻留记忆和细胞毒性程序的增加，这些程序在治疗前就已经活跃，支持快速反应的能力。系统的靶点发现显示，在有反应的患者中，治疗扩大的肿瘤T细胞克隆识别几种自身抗原，包括癌症特异性抗原MAGEA1。治疗还诱导了一种全身免疫反应，其特征是激活的T细胞扩张，富含肿瘤浸润性T细胞克隆型，包括治疗前无法检测到的既有和紧急克隆型。活化的血液CD8 T细胞的频率，特别是治疗前PD-1阳性的KLRG1阴性的T细胞，与肿瘤内的病理反应密切相关。这些结果表明新辅助检查点阻断是如何诱导局部和全身肿瘤免疫的。口腔癌患者对新辅助免疫检查点阻断反应的免疫细胞动力学分析确定了循环和肿瘤浸润性T细胞亚群的不同特征，这些特征是治疗快速反应的基础，并与病理结果相关。
Neoadjuvant immune checkpoint blockade has shown promising clinical activity. Here, we characterized early kinetics in tumor-infiltrating and circulating immune cells in oral cancer patients treated with neoadjuvant anti-PD-1 or anti-PD-1/CTLA-4 in a clinical trial (NCT02919683). Tumor-infiltrating CD8 T cells that clonally expanded during immunotherapy expressed elevated tissue-resident memory and cytotoxicity programs, which were already active prior to therapy, supporting the capacity for rapid response. Systematic target discovery revealed that treatment-expanded tumor T cell clones in responding patients recognized several self-antigens, including the cancer-specific antigen MAGEA1. Treatment also induced a systemic immune response characterized by expansion of activated T cells enriched for tumor-infiltrating T cell clonotypes, including both pre-existing and emergent clonotypes undetectable prior to therapy. The frequency of activated blood CD8 T cells, notably pretreatment PD-1-positive KLRG1-negative T cells, was strongly associated with intra-tumoral pathological response. These results demonstrate how neoadjuvant checkpoint blockade induces local and systemic tumor immunity. Analysis of immune cell kinetics in oral cancer patients responding to neoadjuvant immune checkpoint blockade identifies diverse features in circulating and tumor-infiltrating T cell subpopulations that underlie rapid response to therapy and correlate with pathological outcome.
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
32.4
作者：
Ferretti AP;Kula T;Wang Y;Nguyen DMV;Weinheimer A;Dunlap GS;Xu Q;Nabilsi N;Perullo CR;Cristofaro AW;Whitton HJ;Virbasius A;Olivier KJ Jr;Buckner LR;Alistar AT;Whitman ED;Bertino SA;Chattopadhyay S;MacBeath G
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MacBeath G
影响因子：
82.9
作者：
Fairfax BP;Taylor CA;Watson RA;Nassiri I;Danielli S;Fang H;Mahé EA;Cooper R;Woodcock V;Traill Z;Al-Mossawi MH;Knight JC;Klenerman P;Payne M;Middleton MR
通讯作者：
Middleton MR
影响因子：
8
作者：
Fransen, Marieke F.;Schoonderwoerd, Mark;Ossendorp, Ferry
通讯作者：
Ossendorp, Ferry
影响因子：
10.9
作者：
Banchereau R;Chitre AS;Scherl A;Wu TD;Patil NS;de Almeida P;Kadel Iii EE;Madireddi S;Au-Yeung A;Takahashi C;Chen YJ;Modrusan Z;McBride J;Nersesian R;El-Gabry EA;Robida MD;Hung JC;Kowanetz M;Zou W;McCleland M;Caplazi P;Eshgi ST;Koeppen H;Hegde PS;Mellman I;Mathews WR;Powles T;Mariathasan S;Grogan J;O'Gorman WE
通讯作者：
O'Gorman WE