Regulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-tumor T Cell Responses.
Regulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-tumor T Cell Responses.
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DOI：
10.1016/j.immuni.2015.08.006
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发表时间：
2015-09-15
期刊：
影响因子：
32.4
通讯作者：
Jacks T
中科院分区：
文献类型：
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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
调节性T（Treg）细胞向许多肿瘤类型中的浸润与患者预后差相关。然而，肿瘤内Treg细胞功能的机制仍有待阐明。我们研究了Treg细胞在基因工程小鼠肺腺癌模型中的功能，发现Treg细胞抑制肿瘤相关三级淋巴结构（TA-TLS）中的抗肿瘤反应。TA-TLS已在人类肺癌中被描述，但其功能仍有待确定。该模型中的TLS与>90%的肿瘤在空间上相关，并促进T细胞和肿瘤抗原呈递树突状细胞（DC）之间的相互作用。在Treg细胞耗竭后，TA-TLS中DC的共刺激配体表达和T细胞增殖率增加，导致肿瘤破坏。因此，我们提出TA-TLS中的Treg细胞可以抑制针对肿瘤的内源性免疫反应，靶向这些细胞可能为癌症患者提供治疗益处。
Infiltration of regulatory T (Treg) cells into many tumor types correlates with poor patient prognoses. However, mechanisms of intratumoral Treg cell function remain to be elucidated. We investigated Treg cell function in a genetically-engineered mouse lung adenocarcinoma model and found Treg cells suppress anti-tumor responses in tumor-associated tertiary lymphoid structures (TA-TLS). TA-TLS have been described in human lung cancers, but their function remains to be determined. TLS in this model were spatially associated with >90% of tumors and facilitated interactions between T cells and tumor-antigen presenting dendritic cells (DCs). Costimulatory ligand expression by DCs and T cell proliferation rates increased in TA-TLS upon Treg cell depletion, leading to tumor destruction. Thus, we propose Treg cells in TA-TLS can inhibit endogenous immune responses against tumors, and targeting these cells may provide therapeutic benefit for cancer patients.