Interferon-γ (IFN-γ)

Introduction to IFN-γ

Endogenously produced IFN-γ forms the basis of a tumor surveillance system against the development of primary chemically induced sarcomas. Furthermore, it plays a protective role against infection by protozoan parasites. It enhances phagocyte activity, resulting in the elimination of extracellular bacteria and protozoan parasites.

Fig.1 Immunomodulatory effects of interferon-gamma (IFN-γ). (Castro, 2018)

IFN-γ, γδ T Cells, and Tumor

In mice, γδ T cells are an important early source of tumor-induced IFN-γ, and the expression of IFN-γ may be essential for optimal antitumor responses by these cells. The early production of IFN-γ by murine γδ T cells can enhance MHCI expression on tumors, as well as enhance CD8+ T cell responses, suggesting that γδ T cells could be important for augmenting downstream adaptive immune responses to tumors. So, early IFN-γ secretion by γδ T cells is important for some antitumor responses in mice.

IFN-γ and Cancer

Despite the evidence demonstrating antitumor responses by γδ T cells, the exact role that these cells play in cancer is not entirely clear. In mice, the absence of γδ T cells sometimes leads to enhanced tumor growth, but in some cases, it leads to a reduction in tumor burden.

γδ T cells can promote, inhibit, or possibly have no significant effect on cancer. A better understanding of the different roles of γδ T cells and their secreted factors in cancer can promote a better manipulation of these cells for immunotherapy. Peripheral γδ T cells from breast cancer patients produce enhanced amounts of TNF-α compared with healthy controls, which is thought to be beneficial.

However, peripheral γδ T cells from patients with nasopharyngeal cancer and melanoma produce reduced amounts of IFN-γ and TNF-α, which could contribute to defective antitumor immune responses in these patients.

IFN-γ and Plasmodium Infection

After Plasmodium infection, increased IFN-γ production by various types of cells is involved not only in protective immunity but also in immunopathology. IFN-γ acts as a pro-inflammatory cytokine to induce not only the activation of macrophages but also the generation of uncommon myelolymphoid progenitor cells after Plasmodium infection. γδ T cells express CD40 ligand and produce IFN-γ after Plasmodium infection, resulting in the enhancement of dendritic cell activation as a part of the immune responses to eliminate Plasmodium parasites.

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Reference

1. Castro, Flávia.; et al. Interferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion. Frontiers in Immunology. 2018, 9: 847.