CD83 expression characterizes precursor exhausted T cell population.
CD83 expression characterizes precursor exhausted T cell population.
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CD83 表达是前体耗尽 T 细胞群的特征。
DOI：
10.1038/s42003-023-04631-6
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发表时间：
2023-03-11
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
T细胞耗竭是有效癌症免疫治疗的主要障碍。耗竭的T细胞包括维持增殖能力的亚群，称为前体耗竭的T细胞（TPEX）。虽然TPEX在功能上不同且对于抗肿瘤免疫很重要，但其与异质性肿瘤浸润性T淋巴细胞（TIL）内的其他T细胞亚群具有一些重叠的表型特征。在这里，我们使用嵌合抗原受体（CAR）工程化T细胞治疗的肿瘤模型探索TPEX特有的表面标志物谱。我们发现，与CCR 7-PD 1+（终末分化）和CAR阴性（旁观者）T细胞相比，CD 83主要在CCR 7 + PD 1+肿瘤内CAR-T细胞中表达。与CD 83- T细胞相比，CD 83 + CCR 7 + CAR-T细胞表现出上级抗原诱导的增殖和IL-2产生。此外，我们证实了在原代TIL样品中CCR 7 + PD 1 + T细胞群体中CD 83的选择性表达。我们的研究结果确定了CD 83作为区分TPEX与终末衰竭和旁观者TIL的标志物。CD 83是免疫球蛋白超家族的成员，是区分前体耗竭T细胞与终末耗竭和旁观者肿瘤浸润T淋巴细胞的新标志物。
T cell exhaustion is a main obstacle against effective cancer immunotherapy. Exhausted T cells include a subpopulation that maintains proliferative capacity, referred to as precursor exhausted T cells (TPEX). While functionally distinct and important for antitumor immunity, TPEX possess some overlapping phenotypic features with the other T-cell subsets within the heterogeneous tumor-infiltrating T-lymphocytes (TIL). Here we explore surface marker profiles unique to TPEX using the tumor models treated by chimeric antigen receptor (CAR)-engineered T cells. We find that CD83 is predominantly expressed in the CCR7+PD1+ intratumoral CAR-T cells compared with the CCR7-PD1+ (terminally differentiated) and CAR-negative (bystander) T cells. The CD83+CCR7+ CAR-T cells exhibit superior antigen-induced proliferation and IL-2 production compared with the CD83- T cells. Moreover, we confirm selective expression of CD83 in the CCR7+PD1+ T-cell population in primary TIL samples. Our findings identify CD83 as a marker to discriminate TPEX from terminally exhausted and bystander TIL. CD83, a member of the immunoglobulin superfamily, is a novel marker to discriminate precursor exhausted T cells from terminally exhausted and bystander tumor-infiltrating T-lymphocytes.
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影响因子：
64.8
作者：
Im SJ;Hashimoto M;Gerner MY;Lee J;Kissick HT;Burger MC;Shan Q;Hale JS;Lee J;Nasti TH;Sharpe AH;Freeman GJ;Germain RN;Nakaya HI;Xue HH;Ahmed R
通讯作者：
Ahmed R
影响因子：
64.5
作者：
Good CR;Aznar MA;Kuramitsu S;Samareh P;Agarwal S;Donahue G;Ishiyama K;Wellhausen N;Rennels AK;Ma Y;Tian L;Guedan S;Alexander KA;Zhang Z;Rommel PC;Singh N;Glastad KM;Richardson MW;Watanabe K;Tanyi JL;O'Hara MH;Ruella M;Lacey SF;Moon EK;Schuster SJ;Albelda SM;Lanier LL;Young RM;Berger SL;June CH
通讯作者：
June CH
影响因子：
32.4
作者：
Ebert, Peter J. R.;Cheung, Jeanne;Mellman, Ira
通讯作者：
Mellman, Ira
影响因子：
5.4
作者：
Grayson, Jason M.;Weant, Ashley E.;Hildeman, David
通讯作者：
Hildeman, David
影响因子：
15.9
作者：
Baitsch, Lukas;Baumgaertner, Petra;Speiser, Daniel E.
通讯作者：
Speiser, Daniel E.