The roles of mast cells in anticancer immunity.
The roles of mast cells in anticancer immunity.
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DOI：
10.1007/s00262-012-1246-0
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发表时间：
2012-09
影响因子：
5.8
通讯作者：
Noelle, Randolph J.
中科院分区：
文献类型：
--
作者：
Dalton, Dyana K.;Noelle, Randolph J.
肿瘤微环境（TME）由内皮细胞、成纤维细胞和免疫细胞等基质细胞组成，提供了促进肿瘤生长和侵袭的支持性生态位。 TME 还为有效的抗肿瘤免疫反应设置了免疫抑制屏障，因此正在成为癌症免疫疗法的目标。肥大细胞 (MC) 在早期阶段在 TME 中积聚，它们在 TME 中的存在与许多侵袭性人类癌症的不良预后相关。 MC 在癌症中的一些明确的作用是促进血管生成和肿瘤侵入周围组织。几种诱导性和自发性癌症的小鼠模型表明，MC 是最早在 TME 内积累并形成 TME 的免疫细胞之一。尽管 MC 和其他抑制性骨髓细胞与人类癌症的不良预后相关，但高密度的瘤内效应 T (Teff) 细胞与良好的预后相关。后一个发现激发了人们对开发增加瘤内 T 细胞密度的疗法的兴趣。然而，人们对促进 TME 内肿瘤内 Teff 细胞高密度的细胞和分子机制知之甚少。新证据表明，MC 对于形成免疫抑制性 TME 以及损害抗肿瘤 Teff 细胞反应和瘤内 T 细胞积累至关重要。 MC 的这些作用值得进一步阐明，以提高抗肿瘤免疫力。在这里，我们将总结 TME 中 MC 在人类癌症中的预后意义的临床研究，以及小鼠癌症模型中的研究，这些研究揭示了 MC 如何被招募到 TME 以及 MC 如何促进肿瘤生长。此外，我们将总结我们最近的研究，表明 MC 会损害保护性抗肿瘤 T 细胞反应的产生和瘤内 Teff 细胞的积累。我们还将重点介绍一些针对 TME 中 MC 的方法，以释放抗肿瘤细胞毒性。
The tumor microenvironment (TME), which is composed of stromal cells such as endothelial cells, fibroblasts, and immune cells, provides a supportive niche promoting the growth and invasion of tumors. The TME also raises an immunosuppressive barrier to effective antitumor immune responses and is therefore emerging as a target for cancer immunotherapies. Mast cells (MCs) accumulate in the TME at early stages, and their presence in the TME is associated with poor prognosis in many aggressive human cancers. Some well-established roles of MCs in cancer are promoting angiogenesis and tumor invasion into surrounding tissues. Several mouse models of inducible and spontaneous cancer show that MCs are among the first immune cells to accumulate within and shape the TME. Although MCs and other suppressive myeloid cells are associated with poor prognosis in human cancers, high densities of intratumoral T effector (Teff) cells are associated with a favorable prognosis. The latter finding has stimulated interest in developing therapies to increase intratumoral T cell density. However, cellular and molecular mechanisms promoting high densities of intra-tumoral Teff cells within the TME are poorly understood. New evidence suggests that MCs are essential for shaping the immune-suppressive TME and impairing both antitumor Teff cell responses and intratumoral T cell accumulation. These roles for MCs warrant further elucidation in order to improve antitumor immunity. Here, we will summarize clinical studies of the prognostic significance of MCs within the TME in human cancers, as well as studies in mouse models of cancer that reveal how MCs are recruited to the TME and how MCs facilitate tumor growth. Also, we will summarize our recent studies indicating that MCs impair generation of protective antitumor T cell responses and accumulation of intratumoral Teff cells. We will also highlight some approaches to target MCs in the TME in order to unleash antitumor cytotoxicity.
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DOI：
10.1111/j.1600-6143.2009.02755.x
发表时间：
2009-10
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
de Vries VC;Wasiuk A;Bennett KA;Benson MJ;Elgueta R;Waldschmidt TJ;Noelle RJ
通讯作者：
Noelle RJ
影响因子：
10.5
作者：
Coussens, LM;Raymond, WW;Hanahan, D
通讯作者：
Hanahan, D
影响因子：
3.4
作者：
Esposito, I;Menicagli, M;Campani, D
通讯作者：
Campani, D
影响因子：
11.2
作者：
Camus, Matthieu;Tosolini, Marie;Galon, Jerome
通讯作者：
Galon, Jerome
影响因子：
100.3
作者：
Galli, Stephen J.;Grimbaldeston, Michele;Tsai, Mindy
通讯作者：
Tsai, Mindy