Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses.
Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses.
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DOI：
10.1016/j.cell.2021.11.007
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发表时间：
2021-12-09
期刊：
影响因子：
64.5
通讯作者：
Joshi NS
中科院分区：
文献类型：
--
作者：
Cui C;Wang J;Fagerberg E;Chen PM;Connolly KA;Damo M;Cheung JF;Mao T;Askari AS;Chen S;Fitzgerald B;Foster GG;Eisenbarth SC;Zhao H;Craft J;Joshi NS
CD4 T滤泡辅助细胞（TFH）支持B细胞，这对生发中心（GC）的形成至关重要，但TFH-B细胞相互作用在癌症中的重要性尚不清楚。我们发现，在肺腺癌（LUAD）患者中，TFH细胞转录特征的富集与GC B细胞特征和延长生存期相关。我们进一步建立了小鼠LUAD模型，其中肿瘤细胞表达b细胞和t细胞识别的新抗原。肿瘤特异性TFH和GC B细胞之间的相互作用，以及主要由TFH细胞产生的IL-21，是肿瘤控制和CD8 T细胞功能的必要条件。TFH细胞的发育需要B细胞和B细胞识别的新抗原。因此，肿瘤新抗原可以通过促进肿瘤特异性CD4 T细胞与肿瘤特异性B细胞的相互作用来调节肿瘤特异性CD4 T细胞的命运，从而通过增强CD8 T细胞效应功能来促进抗肿瘤免疫。生发中心B细胞以新抗原依赖的方式促进肿瘤特异性CD4 T滤泡辅助细胞的发展，进而通过产生IL-21增强CD8 T细胞效应功能，并在小鼠肺腺癌模型中驱动抗肿瘤免疫。
CD4 T follicular helper (TFH) cells support B cells, which is critical for germinal center (GC) formation, but the importance of TFH-B cell interactions in cancer is unclear. We found enrichment of TFH cell transcriptional signature correlates with GC B cell signature and with prolonged survival in patients with lung adenocarcinoma (LUAD). We further developed a murine LUAD model in which tumor cells express B-cell- and T-cell-recognized neoantigens. Interactions between tumor-specific TFH and GC B cells, as well as IL-21 primarily produced by TFH cells, are necessary for tumor control and effector CD8 T cell function. Development of TFH cells requires B cells and B-cell-recognized neoantigens. Thus, tumor neoantigens can regulate the fate of tumor-specific CD4 T cells by facilitating their interactions with tumor-specific B cells, which in turn promote anti-tumor immunity by enhancing CD8 T cell effector functions. Germinal center B cells promote the development of tumor-specific CD4 T follicular helper cells in a neoantigen-dependent manner, which in turn enhance CD8 T cell effector functions by producing IL-21 and drive anti-tumor immunity in a murine model of lung adenocarcinoma.
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DOI：
10.1126/science.aao3859
发表时间：
2018-04-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Burnett DL;Langley DB;Schofield P;Hermes JR;Chan TD;Jackson J;Bourne K;Reed JH;Patterson K;Porebski BT;Brink R;Christ D;Goodnow CC
通讯作者：
Goodnow CC
影响因子：
32.4
作者：
Choi YS;Kageyama R;Eto D;Escobar TC;Johnston RJ;Monticelli L;Lao C;Crotty S
通讯作者：
Crotty S
影响因子：
46.9
作者：
Damo M;Fitzgerald B;Lu Y;Nader M;William I;Cheung JF;Connolly KA;Foster GG;Akama-Garren E;Lee DY;Chang GP;Gocheva V;Schmidt LM;Boileve A;Wilson JH;Cui C;Monroy I;Gokare P;Cabeceiras P;Jacks T;Joshi NS
通讯作者：
Joshi NS
影响因子：
64.8
作者：
Cabrita, Rita;Lauss, Martin;Jonsson, Goran
通讯作者：
Jonsson, Goran
影响因子：
4.6
作者：
Akama-Garren, Elliot H.;Joshi, Nikhil S.;Jacks, Tyler
通讯作者：
Jacks, Tyler