Tumor-derived γδ regulatory T cells suppress innate and adaptive immunity through the induction of immunosenescence.
Tumor-derived γδ regulatory T cells suppress innate and adaptive immunity through the induction of immunosenescence.
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DOI：
10.4049/jimmunol.1202369
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发表时间：
2013-03-01
期刊：
影响因子：
--
通讯作者：
Peng G
中科院分区：
文献类型：
--
作者：
Ye J;Ma C;Hsueh EC;Eickhoff CS;Zhang Y;Varvares MA;Hoft DF;Peng G
从根本上理解肿瘤浸润性调节性T细胞（Treg）的不同亚群所利用的抑制机制对于开发有效的抗肿瘤免疫治疗策略至关重要。最近已经在包括癌症的人类疾病中鉴定了γδ Treg细胞。然而，这种新的非常规Treg细胞亚群的抑制机制和功能调节在很大程度上是未知的。在当前的研究中，我们探索了乳腺肿瘤源性γδ Treg细胞对先天性和适应性免疫的抑制机制。我们发现，γδ Treg细胞诱导靶向幼稚T细胞和效应T细胞以及树突状细胞（DC）中的免疫衰老。此外，γδ Treg细胞诱导的衰老T细胞和DC表型改变，功能受损，并产生强抑制活性，进一步增强了γδ Treg细胞介导的免疫抑制作用。此外，我们证明了在γδ Treg细胞中操纵TLR8信号传导可以在体外和体内阻断γδ Treg诱导的T细胞和DC向衰老细胞的转化。我们的研究确定了肿瘤源性γδ Treg细胞介导的对先天性和获得性免疫的新抑制机制，这对于开发强大的创新方法来逆转肿瘤抑制微环境和改善免疫治疗效果至关重要。
Fundamentally understanding the suppressive mechanisms utilized by different subsets of tumor-infiltrating regulatory T (Treg) cells is critical for the development of effective strategies for anti-tumor immunotherapy. γδ Treg cells have recently been identified in human diseases including cancer. However, the suppressive mechanisms and functional regulations of this new subset of unconventional Treg cells are largely unknown. In the current studies, we explored the suppressive mechanism(s) utilized by breast tumor-derived γδ Treg cells on innate and adaptive immunity. We found that γδ Treg cells induced immunosenescence in the targeted naïve and effector T cells, as well as dendritic cells (DCs). Furthermore, senescent T cells and DCs induced by γδ Treg cells had altered phenotypes, impaired functions and developed potent suppressive activities, further amplifying the immunosuppression mediated by γδ Treg cells. In addition, we demonstrated that manipulation of TLR8 signaling in γδ Treg cells can block γδ Treg-induced conversion of T cells and DCs into senescent cells in vitro and in vivo. Our studies identify the novel suppressive mechanism mediated by tumor-derived γδ Treg cells on innate and adaptive immunity, which should be critical for the development of strong and innovative approaches to reverse the tumor suppressive microenvironment and improve effects of immunotherapy.
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影响因子：
11.2
作者：
Dieli F;Vermijlen D;Fulfaro F;Caccamo N;Meraviglia S;Cicero G;Roberts A;Buccheri S;D'Asaro M;Gebbia N;Salerno A;Eberl M;Hayday AC
通讯作者：
Hayday AC
影响因子：
16.8
作者：
Chen WH;Kozlovsky BF;Effros RB;Grubeck-Loebenstein B;Edelman R;Sztein MB
通讯作者：
Sztein MB
影响因子：
4.4
作者：
Kapp, JA;Kapp, LM;McKenna, KC
通讯作者：
McKenna, KC
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
5.8
作者：
Kobayashi, Hirohito;Tanaka, Yoshimasa;Toma, Hiroshi
通讯作者：
Toma, Hiroshi