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Review
. 2011;7(5):651-8.
doi: 10.7150/ijbs.7.651. Epub 2011 May 21.

Dual roles of immune cells and their factors in cancer development and progression

Brian F Zamarron  1 , WanJun Chen
Affiliations
Review

Dual roles of immune cells and their factors in cancer development and progression

Brian F Zamarron et al. Int J Biol Sci. 2011.

Abstract

Traditional wisdom holds that intact immune responses, such as immune surveillance or immunoediting, are required for preventing and inhibiting tumor development; but recent evidence has also indicated that unresolved immune responses, such as chronic inflammation, can promote the growth and progression of cancer. Within the immune system, cytotoxic CD8(+) and CD4(+) Th1 T cells, along with their characteristically produced cytokine IFN-γ, function as the major anti-tumor immune effector cells, whereas tumor associated macrophages (TAM) or myeloid-derived suppressive cells (MDSC) and their derived cytokines IL-6, TNF, IL-1β and IL-23 are generally recognized as dominant tumor-promoting forces. However, the roles played by Th17 cells, CD4(+) CD25(+) Foxp3(+) regulatory T lymphocytes and immunoregulatory cytokines such as TGF-β in tumor development and survival remain elusive. These immune cells and the cellular factors produced from them, including both immunosuppressive and inflammatory cytokines, play dual roles in promoting or discouraging cancer development, and their ultimate role in cancer progression may rely heavily on the tumor microenvironment and the events leading to initial propagation of carcinogenesis.

Keywords: Hepatocellular Carcinoma; TGF-β; Treg; Tumor Associated Macrophages.

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Conflict of interest statement

Conflict of Interests: The authors have declared that no conflict of interest exists.

Figures

Figure 1
Figure 1
A proposed model of chronic inflammation progressing to tumor formation. A chronic insult such as autoimmunity or infection leads to a steady inflamed tissue state. Tumor-associated macrophages (TAM) of the M1 variety begin to produce cytokines that promote Th17 cell differentiation from naïve CD4+ T lymphocytes such as IL-6, IL-23, IL-1β and TNF-α. One of the key cytokines produced by M2 TAM is TGF-β, which may further encourage Th17 development. Myeloid-derived suppressor cells serve an immunosuppressive role within the microenvironment by producing TGF-β as well as other regulatory factors, but may also encourage further Th17 differentiation by secreting IL-6. The production of TGF-β would likely also have the effect of inducing CD4+Foxp3+Tregs within the tumor microenvironment while also suppressing inflammatory cytokine production from the TAM themselves. However, these combined suppressive signals may not be sufficient to overcome the self-perpetuating cycle of activation established between Th17 cells and TAM. At the same time, this suppressive environment may greatly hamper, or even eliminate, the possibility for Th1 and CD8+ T cells to mount an immune response. The net effect of these cellular interactions within the tumor microenvironment is to limit anti-tumor immunity from Th1 and CD8 T cells while continuing to encourage chronic inflammation, angiogenesis, and overall cancer cell survival and proliferation.
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