Treg Depletion Licenses T Cell-Driven HEV Neogenesis and Promotes Tumor Destruction.
Treg Depletion Licenses T Cell-Driven HEV Neogenesis and Promotes Tumor Destruction.
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DOI：
10.1158/2326-6066.cir-17-0131
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发表时间：
2017-11
影响因子：
10.1
通讯作者：
Gallimore A
中科院分区：
文献类型：
--
作者：
Colbeck EJ;Jones E;Hindley JP;Smart K;Schulz R;Browne M;Cutting S;Williams A;Parry L;Godkin A;Ware CF;Ager A;Gallimore A
T细胞浸润到肿瘤中代表了免疫介导的癌症控制的关键瓶颈。 ES（HEVS）。致癌物诱导的肿瘤模型，该模型允许肿瘤微环境和免疫响应的共同进化，这表明Treg的依赖性不仅会导致淋巴结中的HEV网络（LNS）中的HEV网络造成的宽度破坏，而且会激活CD8+ T细胞，然后激活CD8+ T细胞，并驱动了这些因素上的开发。 F受体，独立于淋巴毒素β受体介导的信号。这些肿瘤内HEV不表达趋化因子CCll21，揭示了一个未描述的肿瘤内血管表型，我们提出了一个模型。
T-cell infiltration into tumors represents a critical bottleneck for immune-mediated control of cancer. We previously showed that this bottleneck can be overcome by depleting immunosuppressive Foxp3+ regulatory T cells (Tregs), a process which can increase frequencies of tumor-infiltrating lymphocytes (TILs) through promoting development of specialized portals for lymphocyte entry, namely high endothelial venules (HEVs). In this paper, we used a carcinogen-induced tumor model, that allows for co-evolution of the tumor microenvironment and the immune response, to demonstrate that Treg depletion not only results in widespread disruption to HEV networks in lymph nodes (LNs) but activates CD8+ T cells, which then drive intratumoral HEV development. Formation of these vessels contrasts with ontogenic HEV development in LNs in that the process is dependent on TNF receptor and independent of lymphotoxin β receptor-mediated signaling. These intratumoral HEVs do not express the chemokine CCL21, revealing a previously undescribed intratumoral blood vessel phenotype. We propose a model where Treg depletion enables a self-amplifying loop of T-cell activation, which promotes HEV development, T-cell infiltration, and ultimately, tumor destruction. The findings point to a need to test for HEV development as part of ongoing clinical studies in patients with cancer.
影响因子：
6.4
作者：
Ondondo, Beatrice;Jones, Emma;Hindley, James;Cutting, Scott;Smart, Kathryn;Bridgeman, Hayley;Matthews, Katherine K.;Ladell, Kristin;Price, David A.;Jackson, David G.;Godkin, Andrew;Ager, Ann;Gallimore, Awen
通讯作者：
Gallimore, Awen