Induction of anergic or regulatory tumor-specific CD4(+) T cells in the tumor-draining lymph node.
Induction of anergic or regulatory tumor-specific CD4(+) T cells in the tumor-draining lymph node.
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DOI：
10.1038/s41467-018-04524-x
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发表时间：
2018-05-29
影响因子：
16.6
通讯作者：
Lantz O
中科院分区：
文献类型：
--
作者：
Alonso R;Flament H;Lemoine S;Sedlik C;Bottasso E;Péguillet I;Prémel V;Denizeau J;Salou M;Darbois A;Núñez NG;Salomon B;Gross D;Piaggio E;Lantz O
CD4+ T细胞抗肿瘤应答主要在表达分泌型抗原（Ags）的移植肿瘤中进行研究，而人类癌症中的大多数突变蛋白不分泌。在携带自体肿瘤的小鼠中，识别胞质Ag的Ag特异性CD4+ T细胞的命运仍不清楚。在这里，我们显示，使用基因工程肺腺癌小鼠模型，初始肿瘤特异性CD4+ T细胞在肿瘤引流淋巴结（TdLN）中被激活和增殖，但不分化为效应细胞或在肿瘤中积累。相反，这些CD4+ T细胞从肿瘤发展的早期阶段被驱动朝向无反应性或外周诱导的Treg（pTreg）分化。这种对免疫抑制的偏好仅限于TdLN，并由富含肿瘤Ag特异性细胞群的TdLN维持。因此，肿瘤可能通过重演外周自身耐受机制，在TdLN中实施抗肿瘤CD4应答的显性抑制。肿瘤新抗原可以引流到淋巴结，但诱导的免疫应答的性质和意义仍不清楚。在这里，作者使用小鼠遗传肿瘤模型来表明肿瘤特异性CD4 T细胞可以在引流淋巴结中变得无反应性或抑制性，以调节肿瘤免疫。
CD4+ T cell antitumor responses have mostly been studied in transplanted tumors expressing secreted model antigens (Ags), while most mutated proteins in human cancers are not secreted. The fate of Ag-specific CD4+ T cells recognizing a cytoplasmic Ag in mice bearing autochthonous tumors is still unclear. Here we show, using a genetically engineered lung adenocarcinoma mouse model, that naive tumor-specific CD4+ T cells are activated and proliferate in the tumor-draining lymph node (TdLN) but do not differentiate into effectors or accumulate in tumors. Instead, these CD4+ T cells are driven toward anergy or peripherally-induced Treg (pTreg) differentiation, from the early stage of tumor development. This bias toward immune suppression is restricted to the TdLN, and is maintained by Tregs enriched in the tumor Ag-specific cell population. Thus, tumors may enforce a dominant inhibition of the anti-tumor CD4 response in the TdLN by recapitulating peripheral self-tolerance mechanisms. Tumor neoantigens can be drained to the lymph nodes, but the nature and the significance of the induced immune responses are still unclear. Here the authors use a mouse genetic tumor model to show that tumor-specific CD4 T cells can become anergic or suppressive in the draining lymph node to modulate tumor immunity.
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影响因子：
32.4
作者：
Hill, Jonathan A.;Feuerer, Markus;Benoist, Christophe
通讯作者：
Benoist, Christophe
影响因子：
8.8
作者：
Nutsch K;Chai JN;Ai TL;Russler-Germain E;Feehley T;Nagler CR;Hsieh CS
通讯作者：
Hsieh CS
DOI：
10.1084/jem.176.2.553
发表时间：
1992-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guerder S;Matzinger P
通讯作者：
Matzinger P
影响因子：
32.4
作者：
Joshi NS;Akama-Garren EH;Lu Y;Lee DY;Chang GP;Li A;DuPage M;Tammela T;Kerper NR;Farago AF;Robbins R;Crowley DM;Bronson RT;Jacks T
通讯作者：
Jacks T
影响因子：
30.5
作者：
Lantz, O;Grandjean, I;Di Santo, JP
通讯作者：
Di Santo, JP