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Targeting macrophage anti-tumor activity to suppress melanoma progression

View Article: PubMed Central - PubMed

ABSTRACT

By phagocytosing cancer cells and their cellular debris, macrophages play a critical role in nonspecific defense (innate immunity) and, as antigen presenters, they help initiate specific defense mechanisms (adaptive immunity). Malignant melanoma is a lethal disease due to its aggressive capacity for metastasis and resistance to therapy. For decades, considerable effort has gone into development of an effective immunotherapy for treatment of metastatic melanoma. In this review, we focus on the anti-tumor activities of macrophages in melanoma and their potential as therapeutic targets in melanoma. Although macrophages can be re-educated through intercellular signaling to promote tumor survival owing to their plasticity, we expect that targeting the anti-tumor activity of macrophages remains a promising strategy for melanoma inhibition. The combination of tumoricidal macrophage activation and other treatments such as surgery, chemotherapy, and radiotherapy, may provide an effective and comprehensive anti-melanoma strategy.

No MeSH data available.


Related in: MedlinePlus

Biphasic effects of IFN-γ on melanomaApplication of IFN-γ to melanoma treatment (Left). Adverse effects of IFN-γ on melanoma by pro-expression of MHC-I or CD74 (Right).
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Figure 4: Biphasic effects of IFN-γ on melanomaApplication of IFN-γ to melanoma treatment (Left). Adverse effects of IFN-γ on melanoma by pro-expression of MHC-I or CD74 (Right).

Mentions: IFN-γ is the effector cytokine of Th1 helper cells and after Th1 activation macrophages, as the main effector cells of Th1 immunity, are activated to kill microorganisms and tumor cells and produce copious amounts of proinflammatory cytokines (Figure 3). Therefore, administration of IFN-γ suppresses melanoma development by activating macrophages (Figure 4 left). IFN-γ, which can be produced by macrophages, has a direct antitumor effect on melanoma cells [44–47]. IFN-γ plays a role in the response to melanoma indirectly through its effect on the immune system and directly through its anti-proliferative and pro-apoptotic effects on melanoma cells [44]. IFN-γ added to A375 melanoma cells caused an additive growth inhibitory response [45]. The combination of IFN-γ with IFN-α or IFN-β resulted in a strong synergistic anti-proliferative activity on four human melanoma cell lines (StML-11, StML-12, StML-14, and SKMel-28) [46]. The changes in gene expression associated with the direct anti-melanoma effect of IFN-γ were striking, as these involved genes or groups of genes previously implicated in the malignant phenotype of melanoma as well as genes not previously thought to be involved in melanoma growth and survival [47].


Targeting macrophage anti-tumor activity to suppress melanoma progression
Biphasic effects of IFN-γ on melanomaApplication of IFN-γ to melanoma treatment (Left). Adverse effects of IFN-γ on melanoma by pro-expression of MHC-I or CD74 (Right).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5392344&req=5

Figure 4: Biphasic effects of IFN-γ on melanomaApplication of IFN-γ to melanoma treatment (Left). Adverse effects of IFN-γ on melanoma by pro-expression of MHC-I or CD74 (Right).
Mentions: IFN-γ is the effector cytokine of Th1 helper cells and after Th1 activation macrophages, as the main effector cells of Th1 immunity, are activated to kill microorganisms and tumor cells and produce copious amounts of proinflammatory cytokines (Figure 3). Therefore, administration of IFN-γ suppresses melanoma development by activating macrophages (Figure 4 left). IFN-γ, which can be produced by macrophages, has a direct antitumor effect on melanoma cells [44–47]. IFN-γ plays a role in the response to melanoma indirectly through its effect on the immune system and directly through its anti-proliferative and pro-apoptotic effects on melanoma cells [44]. IFN-γ added to A375 melanoma cells caused an additive growth inhibitory response [45]. The combination of IFN-γ with IFN-α or IFN-β resulted in a strong synergistic anti-proliferative activity on four human melanoma cell lines (StML-11, StML-12, StML-14, and SKMel-28) [46]. The changes in gene expression associated with the direct anti-melanoma effect of IFN-γ were striking, as these involved genes or groups of genes previously implicated in the malignant phenotype of melanoma as well as genes not previously thought to be involved in melanoma growth and survival [47].

View Article: PubMed Central - PubMed

ABSTRACT

By phagocytosing cancer cells and their cellular debris, macrophages play a critical role in nonspecific defense (innate immunity) and, as antigen presenters, they help initiate specific defense mechanisms (adaptive immunity). Malignant melanoma is a lethal disease due to its aggressive capacity for metastasis and resistance to therapy. For decades, considerable effort has gone into development of an effective immunotherapy for treatment of metastatic melanoma. In this review, we focus on the anti-tumor activities of macrophages in melanoma and their potential as therapeutic targets in melanoma. Although macrophages can be re-educated through intercellular signaling to promote tumor survival owing to their plasticity, we expect that targeting the anti-tumor activity of macrophages remains a promising strategy for melanoma inhibition. The combination of tumoricidal macrophage activation and other treatments such as surgery, chemotherapy, and radiotherapy, may provide an effective and comprehensive anti-melanoma strategy.

No MeSH data available.


Related in: MedlinePlus