CD8(+) T cell activation in cancer comprises an initial activation phase in lymph nodes followed by effector differentiation within the tumor.
CD8(+) T cell activation in cancer comprises an initial activation phase in lymph nodes followed by effector differentiation within the tumor.
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DOI：
10.1016/j.immuni.2022.12.002
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发表时间：
2023-01-10
期刊：
影响因子：
32.4
通讯作者：
Kissick, Haydn
中科院分区：
文献类型：
--
作者：
Prokhnevska, Nataliya;Cardenas, Maria A.;Valanparambil, Rajesh M.;Sobierajska, Ewelina;Barwick, Benjamin G.;Jansen, Caroline;Moon, Adriana Reyes;Gregorova, Petra;delBalzo, Luke;Greenwald, Rachel;Bilen, Mehmet Asim;Alemozaffar, Mehrdad;Joshi, Shreyas;Cimmino, Cara;Larsen, Christian;Master, Viraj;Sanda, Martin;Kissick, Haydn
肿瘤免疫治疗的改善取决于对抗肿瘤T细胞应答的更好理解。通过研究人类肿瘤引流淋巴结（TDLN），我们发现TDLN中活化的CD8+ T细胞与肿瘤中的TCF 1+干细胞样细胞共享功能，转录和表观遗传特征。表型和TCR重叠表明这些TDLN细胞是肿瘤驻留干细胞样CD8+ T细胞的前体。小鼠肿瘤模型显示，肿瘤特异性CD8+ T细胞在TDLN中被激活，但缺乏效应表型。这些干细胞样细胞迁移到肿瘤中，其中来自抗原呈递细胞的额外共刺激驱动效应分化。这种响应于癌症的CD8+ T细胞活化的模型不同于经典的CD8+ T细胞活化急性病毒的模型，并且它提出了肿瘤特异性CD8+ T细胞活化的两个阶段：TDLN中的初始活化和在额外的共刺激后肿瘤内的后续效应程序获取。需要更好地理解控制抗肿瘤T细胞应答的基本机制。在这里，Prokhnevska等人描述了对癌症的两步T细胞活化反应：（1）在肿瘤引流淋巴结中的初始引发，导致干细胞样表型和（2）在肿瘤中的共刺激依赖性阶段以获得效应物编程。
Improvements in tumor immunotherapies depend on better understanding of the anti-tumor T cell response. By studying human tumor-draining lymph nodes (TDLNs), we found that activated CD8+ T cells in TDLNs shared functional, transcriptional, and epigenetic traits with TCF1+ stem-like cells in the tumor. The phenotype and TCR overlap suggested that these TDLN cells were precursors to tumor-resident stem-like CD8+ T cells. Murine tumor models revealed that tumor-specific CD8+ T cells were activated in TDLNs but lacked an effector phenotype. These stem-like cells migrated into the tumor, where additional co-stimulation from antigen-presenting cells drove effector differentiation. This model of CD8+ T cell activation in response to cancer is different from that of canonical CD8+ T cell activation to acute viruses, and it proposes two stages of tumor-specific CD8+ T cell activation: initial activation in TDLNs and subsequent effector program acquisition within the tumor after additional co-stimulation. Better understanding of the fundamental mechanisms controlling anti-tumor T cell responses is needed. Here, Prokhnevska et al. describe a two-step T cell activation response to cancer: (1) initial priming in tumor-draining lymph nodes resulting in a stem-like phenotype and (2) a co-stimulation-dependent phase in the tumor to acquire effector programming.
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影响因子：
28.2
作者：
Chen PL;Roh W;Reuben A;Cooper ZA;Spencer CN;Prieto PA;Miller JP;Bassett RL;Gopalakrishnan V;Wani K;De Macedo MP;Austin-Breneman JL;Jiang H;Chang Q;Reddy SM;Chen WS;Tetzlaff MT;Broaddus RJ;Davies MA;Gershenwald JE;Haydu L;Lazar AJ;Patel SP;Hwu P;Hwu WJ;Diab A;Glitza IC;Woodman SE;Vence LM;Wistuba II;Amaria RN;Kwong LN;Prieto V;Davis RE;Ma W;Overwijk WW;Sharpe AH;Hu J;Futreal PA;Blando J;Sharma P;Allison JP;Chin L;Wargo JA
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2.2
作者：
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通讯作者：
Dalod M
影响因子：
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影响因子：
30.5
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影响因子：
10.9
作者：
Buchwald ZS;Nasti TH;Lee J;Eberhardt CS;Wieland A;Im SJ;Lawson D;Curran W;Ahmed R;Khan MK
通讯作者：
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