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. 2018;6(2):34-42.
Epub 2018 Mar 16.

Regulatory T Cells in Gynecologic Cancer

Yang Ou  1 , Martin J Cannon  2 , Mayumi Nakagawa  1
Affiliations

Regulatory T Cells in Gynecologic Cancer

Yang Ou et al. MOJ Immunol. 2018.

Abstract

Increasing evidence supports that regulatory T cells (Tregs) within the tumor, tumor draining lymph nodes, ascites and peripheral blood of patients with cancer are associated with poor prognosis. Tregs are important mediators of active immune evasion in cancer. In this review, the potential mechanisms of Treg actions and the roles of Tregs specifically in the tumor microenvironment derived from three types of gynecological cancers, cervical, vulvar and ovarian, are described. The correlations between Tregs and clinical immunotherapeutic study outcomes are discussed. Successful modulation of Tregs would likely have significant impact on the effectiveness of immunotherapeutic treatments in cancer patients.

Keywords: Tregs; cancer; cervical; ovarian; vulvar.

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Conflict of interest statement

Conflict of interest Mayumi Nakagawa is named as one of the inventors of PepCan in patents and patent applications describing it. Martin Cannon and UAMS have a financial interest through licensed patents in aspects of the technology discussed in this publication. These financial interests have been reviewed and approved in accordance with the UAMS conflict of interest policies.

Figures

Figure 1
Figure 1
Thymic and peripheral generation of Tregs. tTregs are selected by high-avidity interaction between T cell receptors and self-peptide-MHC class II complexes in the thymus. Peripheral Tregs develop outside the thymus under suboptimal antigen presentation. pTregs are derived from naïve CD4+ T cells. In addition, pTregs comprise two additional subsets Tr1 and Th3.
Figure 2
Figure 2
Mechanisms of infiltration and accumulation of Tregs in the tumor microenvironment: (1) Tregs are recruited to tumor from the periphery by chemokines e.g. CCL28 or CCL12; (2) Within the tumor microenvironment Tregs can be expanded by IL-2 administration; (3) Tumor derived TGF-β can covert naïve CD4+ T cells into Tregs.
Figure 3
Figure 3
Mechanisms of Tregs-mediated immunosuppression. Tregs promote tumor progression by (1) inhibition of effector T cell proliferation, lysis of effector T cells through release of granzyme B and perforin, or conversion of CD4+ T cells into Tregs; (2) interactions with DCs through downregulation of CD80/CD86 on DCs or upregulation of indoleamine 2,3-dioxygenase IDO in DCs; (3) inhibition of NK cell function through downregulation of NKG2D on NK cells or direct inhibition of NK proliferation and cytotoxicity.
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