Regulatory T cell subsets in human cancer: are they regulating for or against tumor progression?
Regulatory T cell subsets in human cancer: are they regulating for or against tumor progression?
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DOI：
10.1007/s00262-013-1490-y
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发表时间：
2014-01
影响因子：
5.8
通讯作者：
Whiteside, Theresa L.
中科院分区：
文献类型：
--
作者：
Whiteside, Theresa L.
调节性T细胞（Treg）在维持人类健康和疾病中免疫反应的平衡中起着关键作用。Treg有很多种口味，可以利用各种机制来调节免疫反应。在癌症中，诱导(i)或适应性Treg扩增，在患者的组织和外周血中积累，并代表CD4+ T淋巴细胞的功能突出成分。在表型和功能上，iTreg与天然Treg不同。表达外核苷酶CD39和CD73的iTreg亚群能够将ATP水解为5 ' -AMP和腺苷（ADO），从而介导对表达ADO受体的免疫细胞的抑制。iTeg还能产生前列腺素E2 （PGE2）。这些iTreg在肿瘤抗原和细胞因子（如TGF-β或IL-10）的反应中扩增，可能是抑制抗肿瘤免疫反应和肿瘤成功逃逸的原因。另一方面，在与炎症浸润显著相关的癌症中，如结直肠癌或某些类型的乳腺癌，iTreg通过产生ADO和/或PGE2来下调过度炎症，保护宿主免受组织损伤和肿瘤发展。因此，利用相同腺苷途径的iTreg在癌症中发挥着关键的双重作用，其可塑性受微环境的控制和驱动。因此，监测iTreg而不是nTreg的频率和功能对癌症很重要。此外，在免疫治疗之前通过各种现有策略消除iTreg可能并不对所有病例都有益，需要谨慎进行。
Regulatory T cells (Treg) play a key role in maintaining the balance of immune responses in human health and in disease. Treg come in many flavors and can utilize a variety of mechanisms to modulate immune responses. In cancer, inducible (i) or adaptive Treg expand, accumulate in tissues and the peripheral blood of patients and represent a functionally-prominent component of CD4+ T lymphocytes. Phenotypically and functionally, iTreg are distinct from natural (n) Treg. A subset of iTreg expressing ectonucleotidases, CD39 and CD73, is able to hydrolyze ATP to 5’-AMP and adenosine (ADO) and thus mediate suppression of those immune cells which express ADO receptors. iTeg can also produce prostaglandin E2 (PGE2). These iTreg, expanding in response to tumor antigens and cytokines such as TGF-β or IL-10, are presumably responsible for suppression of anti-tumor immune responses and for successful tumor escape. On the other hand, in cancers associated with prominent inflammatory infiltrates, e.g., colorectal carcinoma or certain types of breast cancer, iTreg down-regulate excessive inflammation by producing ADO and/or PGE2 and protect the host from tissue injury and tumor development. Thus, iTreg utilizing the same adenosine pathway play a key but dual role in cancer, and their plasticity is controlled and driven by the microenvironment. Thus, monitoring for the frequency and functions of iTreg rather than nTreg is important in cancer. In addition, elimination of iTreg by various available strategies prior to immunotherapies may not be beneficial in all cases and needs to be undertaken with caution.
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