TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses.
TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses.
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DOI：
10.1038/s41467-021-22535-z
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发表时间：
2021-04-14
影响因子：
16.6
通讯作者：
Benvenuti F
中科院分区：
文献类型：
--
作者：
Caronni N;Piperno GM;Simoncello F;Romano O;Vodret S;Yanagihashi Y;Dress R;Dutertre CA;Bugatti M;Bourdeley P;Del Prete A;Schioppa T;Mazza EMC;Collavin L;Zacchigna S;Ostuni R;Guermonprez P;Vermi W;Ginhoux F;Bicciato S;Nagata S;Benvenuti F
1 型树突状细胞 (cDC1) 获取细胞相关肿瘤抗原对于通过交叉呈递诱导和维持肿瘤特异性 CD8+ T 细胞至关重要。在这里，我们表明，在小鼠肺部肿瘤的进展过程中，组织驻留肺 cDC1 对细胞相关抗原的捕获和吞噬受到抑制。从机制上讲，吞噬作用的丧失与肿瘤介导的磷脂酰丝氨酸受体 TIM4 下调有关，TIM4 在正常肺驻留 cDC1 中高度表达。 TIM4 受体阻断和条件性 cDC1 缺失会损害肿瘤特异性 CD8+ T 细胞的活化并促进肿瘤进展。在人类肺腺癌中，TIM4 转录物增加了 cDC1 特征的预后价值并预测对 PD-1 治疗的反应。因此，肺驻留 cDC1 上的 TIM4 有助于免疫监视，并且其表达在晚期肿瘤中受到抑制。获取垂死的肿瘤细胞相关抗原是传统 1 型树突状细胞 (cDC1) 启动抗肿瘤免疫反应的重要步骤。作者在此表明，肺肿瘤相关 cDC1 中 TIM4 表达的丧失与晚期肺肿瘤中细胞相关抗原的低效摄取和 CD8 +T 细胞活化的减少有关。
Acquisition of cell-associated tumor antigens by type 1 dendritic cells (cDC1) is essential to induce and sustain tumor specific CD8+ T cells via cross-presentation. Here we show that capture and engulfment of cell associated antigens by tissue resident lung cDC1 is inhibited during progression of mouse lung tumors. Mechanistically, loss of phagocytosis is linked to tumor-mediated downregulation of the phosphatidylserine receptor TIM4, that is highly expressed in normal lung resident cDC1. TIM4 receptor blockade and conditional cDC1 deletion impair activation of tumor specific CD8+ T cells and promote tumor progression. In human lung adenocarcinomas, TIM4 transcripts increase the prognostic value of a cDC1 signature and predict responses to PD-1 treatment. Thus, TIM4 on lung resident cDC1 contributes to immune surveillance and its expression is suppressed in advanced tumors. Acquisition of dying tumor cell-associated antigens is an essential step for the initiation of anti-tumor immune response by conventional type 1 dendritic cells (cDC1). Here the authors show that the loss of TIM4 expression in lung tumor associated cDC1 is associated with less efficient uptake of cell associated antigens and reduction of CD8 + T cell activation in advanced lung tumors.
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影响因子：
28.2
作者：
Dimitrova N;Gocheva V;Bhutkar A;Resnick R;Jong RM;Miller KM;Bendor J;Jacks T
通讯作者：
Jacks T
影响因子：
64.5
作者：
Cubillos-Ruiz JR;Silberman PC;Rutkowski MR;Chopra S;Perales-Puchalt A;Song M;Zhang S;Bettigole SE;Gupta D;Holcomb K;Ellenson LH;Caputo T;Lee AH;Conejo-Garcia JR;Glimcher LH
通讯作者：
Glimcher LH
影响因子：
15.9
作者：
Helft, Julie;Manicassamy, Balaji;Merad, Miriam
通讯作者：
Merad, Miriam
影响因子：
32.4
作者：
Guilliams M;Dutertre CA;Scott CL;McGovern N;Sichien D;Chakarov S;Van Gassen S;Chen J;Poidinger M;De Prijck S;Tavernier SJ;Low I;Irac SE;Mattar CN;Sumatoh HR;Low GHL;Chung TJK;Chan DKH;Tan KK;Hon TLK;Fossum E;Bogen B;Choolani M;Chan JKY;Larbi A;Luche H;Henri S;Saeys Y;Newell EW;Lambrecht BN;Malissen B;Ginhoux F
通讯作者：
Ginhoux F
DOI：
10.1084/jem.20101158
发表时间：
2011-09-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Diamond MS;Kinder M;Matsushita H;Mashayekhi M;Dunn GP;Archambault JM;Lee H;Arthur CD;White JM;Kalinke U;Murphy KM;Schreiber RD
通讯作者：
Schreiber RD