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American Journal of Immunology
Year: 2009  |  Volume: 5  |  Issue: 1  |  Page No.: 17 - 28

The Role of Treg Cells in the Cancer Immunological Response

Zhi-Zhang Yang and Stephen M. Ansell    

Abstract: Problem statement: T cell-mediated immunosuppression has been observed for decades without clarification as to which factor was responsible for this observation. The identification of CD4+CD25+ regulatory T (Treg) cells represents a milestone in the filed of immunology and provides an explanation for T-cell-mediated immunosuppression. Although Treg cells were originally identified for their ability to prevent organ-specific autoimmune disease in mice, emerging evidence suggests that Treg cells play a pivotal role in tumor immunity and contribute to tumor growth and progression, thereby having an important impact on the outcome of cancer patients. Approach: This article reviewed the medical literature to describe how Treg cells affect anti-tumor immunity. Results: Treg cells suppressed anti-tumor immunity by inhibiting the effector functions of tumor-specific T cells and NK cells. Importantly, tumor cells played an active role in recruiting and generating Treg cells and creating a suppressive tumor microenvironment. Strategies to deplete Treg cells or inhibit their function had yielded promising results by enhancing anti-tumor immunity in experimental studies as well as clinical practice. Conclusion: A better understanding of the pathophysiology of Treg cells not only increased our knowledge in a variety of aspects of immunology but also potentially benefited cancer patients.

Figure 1 provides a schematic diagram of tumor-mediated generation of Treg cells and the consequence of elevated Treg cells in tumor microenvironment. Basically, tumor cells induce the generation of Treg cells through both cell contact-dependent and cell contact-independent mechanisms. Soluble proteins such as TGF-β produced by tumor cells promote the proliferation of Treg cells and induce the conversion of naïve CD4+CD25- T cells into Treg cells. Tumor cells also express surface proteins such as CD80/CD86 or CD70 and interact with naïve cells in a cell contact-dependent manner to convert these naïve T cells into Treg cells. In addition to tumor cells, dendritic cells are also able to convert naïve T cells into Treg cells and contribute to the elevated numbers of Treg cells seen in the tumor microenvironment. Elevated numbers of Treg cells participate in creating an immunosuppressive tumor microenvironment by suppressing the innate and adaptive immune responses thereby contributing to the progression of tumors. In contrast to inducing the generation of Treg cells, tumor cells may also inhibit the development of inflammatory immune cells such as TH17 cells. Along with elevated number of Treg cells, an insufficient number of TH17 cells contribute to the inadequate immune response and the limited anti-tumor immunity.


Fig. 1: Tumor-mediated generation of Treg cells and the impact on the tumor microenvironment

 

Strategies that deplete or inhibit Treg cells and thereby promote a competent immune response in the tumor microenvironment should be the goal in future immunotherapeutic studies in cancer patients.

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