Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade.
Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade.
复制标题
肿瘤内CD103+ CD8+ T细胞预测对PD-L1阻断的反应。
DOI：
10.1136/jitc-2020-002231
复制
发表时间：
2021-04
影响因子：
10.9
通讯作者：
O'Gorman WE
中科院分区：
文献类型：
--
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
以CD 103（ITGAE）表达为标志的CD 8+组织驻留记忆T（TRM）细胞被认为可以积极抑制癌症进展，从而导致这样的假设：它们在肿瘤中的存在可能预测对免疫治疗的反应。在这里，我们通过将高维单细胞模式与1868例参与atezolizumab（抗程序性细胞死亡配体1（PD-L1））肺癌和膀胱癌临床试验的患者的大量肿瘤转录组学相结合来测试这一点。ITGAE被鉴定为发炎肿瘤中最显著上调的基因。肿瘤CD 103 + CD 8 + TRM细胞表现出复杂的表型，由检查点调节因子、细胞毒性蛋白的表达和增加的克隆扩增定义。我们的分析确实表明，通过跟踪肿瘤内CD 103表达定量的CD 103 + CD 8 + TRM细胞的存在可以预测治疗结果，这表明对PD-1/PD-L1阻断有反应的患者是那些表现出持续抗肿瘤T细胞反应的患者。
CD8+ tissue-resident memory T (TRM) cells, marked by CD103 (ITGAE) expression, are thought to actively suppress cancer progression, leading to the hypothesis that their presence in tumors may predict response to immunotherapy. Here, we test this by combining high-dimensional single-cell modalities with bulk tumor transcriptomics from 1868 patients enrolled in lung and bladder cancer clinical trials of atezolizumab (anti-programmed cell death ligand 1 (PD-L1)). ITGAE was identified as the most significantly upregulated gene in inflamed tumors. Tumor CD103+ CD8+ TRM cells exhibited a complex phenotype defined by the expression of checkpoint regulators, cytotoxic proteins, and increased clonal expansion. Our analyses indeed demonstrate that the presence of CD103+ CD8+ TRM cells, quantified by tracking intratumoral CD103 expression, can predict treatment outcome, suggesting that patients who respond to PD-1/PD-L1 blockade are those who exhibit an ongoing antitumor T-cell response.
登录
查看更多内容
影响因子：
4
作者：
Gherardin NA;Souter MN;Koay HF;Mangas KM;Seemann T;Stinear TP;Eckle SB;Berzins SP;d'Udekem Y;Konstantinov IE;Fairlie DP;Ritchie DS;Neeson PJ;Pellicci DG;Uldrich AP;McCluskey J;Godfrey DI
通讯作者：
Godfrey DI
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：
64.8
作者：
CEPEK, KL;SHAW, SK;BRENNER, MB
通讯作者：
BRENNER, MB
PD-1和PD-L1抑制剂作为癌症免疫疗法的一种形式的开发：对注册试验和未来考虑的全面综述。
影响因子：
10.9
作者：
Gong J;Chehrazi-Raffle A;Reddi S;Salgia R
通讯作者：
Salgia R
影响因子：
10.1
作者：
Abd Hamid M;Colin-York H;Khalid-Alham N;Browne M;Cerundolo L;Chen JL;Yao X;Rosendo-Machado S;Waugh C;Maldonado-Perez D;Bowes E;Verrill C;Cerundolo V;Conlon CP;Fritzsche M;Peng Y;Dong T
通讯作者：
Dong T