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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

Immunoembolization with tumoricidal macrophage aggregationEmbolization agents combined with GM-CSF are infused by blood vessel to melanoma sites, which results in disruption of the tumor blood supply and the local immunologic reaction evoked by GM-CSF stimulating hepatic macrophages.
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Figure 2: Immunoembolization with tumoricidal macrophage aggregationEmbolization agents combined with GM-CSF are infused by blood vessel to melanoma sites, which results in disruption of the tumor blood supply and the local immunologic reaction evoked by GM-CSF stimulating hepatic macrophages.

Mentions: GM-CSF, as an immunoadjuvant agent, has been used for the embolization of human melanoma. In 2008, a phase I trial that used human recombinant GM-CSF for immuno- embolization was reported [28]. There was no maximum-tolerated, dose-limiting dose or late toxicity found at doses as high as 2000 μg of GM-CSF, and higher doses correlated with longer systemic progression-free survival. A subsequent retrospective analysis that compared immuno- embolization with carmustine chemoembolization showed a significantly longer survival with immuno- embolization [29]. To further investigate the immunologic mechanism and efficacy of this approach, a randomized phase II clinical trial was designed. Immunoembolization with GM-CSF mixed with ethiodized oil was performed on patients with histologically confirmed metastatic uveal melanoma to the liver (contains more than 70% of all tissue macrophages) [30]. The investigators expected that local immunologic reaction evoked by GM-CSF would induce systemic immunity against melanoma cells and delay the development of remote systemic metastases [30]. The working hypothesis of the study was that immuno- embolization would stimulate massive numbers of hepatic macrophages to induce a more robust inflammatory response, triggering a systemic immune recognition of uveal melanoma and delaying the progression of extrahepatic metastasis (Figure 2). These patients showed longer extrahepatic recurrence-free periods, presumably as a result of better immunologic control of circulating micrometastases [30]. The prognosis of patients with uveal melanoma with hepatic metastasis is extremely poor, and the overall survival is generally short: less than 1 year in most cases. Immunoembolization seems to be safe, easy to administer, and potentially effective. The results obtained in the study are encouraging; however, further clinical and basic research is needed to optimize and improve the efficacy of immuno- embolization.


Targeting macrophage anti-tumor activity to suppress melanoma progression
Immunoembolization with tumoricidal macrophage aggregationEmbolization agents combined with GM-CSF are infused by blood vessel to melanoma sites, which results in disruption of the tumor blood supply and the local immunologic reaction evoked by GM-CSF stimulating hepatic macrophages.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Immunoembolization with tumoricidal macrophage aggregationEmbolization agents combined with GM-CSF are infused by blood vessel to melanoma sites, which results in disruption of the tumor blood supply and the local immunologic reaction evoked by GM-CSF stimulating hepatic macrophages.
Mentions: GM-CSF, as an immunoadjuvant agent, has been used for the embolization of human melanoma. In 2008, a phase I trial that used human recombinant GM-CSF for immuno- embolization was reported [28]. There was no maximum-tolerated, dose-limiting dose or late toxicity found at doses as high as 2000 μg of GM-CSF, and higher doses correlated with longer systemic progression-free survival. A subsequent retrospective analysis that compared immuno- embolization with carmustine chemoembolization showed a significantly longer survival with immuno- embolization [29]. To further investigate the immunologic mechanism and efficacy of this approach, a randomized phase II clinical trial was designed. Immunoembolization with GM-CSF mixed with ethiodized oil was performed on patients with histologically confirmed metastatic uveal melanoma to the liver (contains more than 70% of all tissue macrophages) [30]. The investigators expected that local immunologic reaction evoked by GM-CSF would induce systemic immunity against melanoma cells and delay the development of remote systemic metastases [30]. The working hypothesis of the study was that immuno- embolization would stimulate massive numbers of hepatic macrophages to induce a more robust inflammatory response, triggering a systemic immune recognition of uveal melanoma and delaying the progression of extrahepatic metastasis (Figure 2). These patients showed longer extrahepatic recurrence-free periods, presumably as a result of better immunologic control of circulating micrometastases [30]. The prognosis of patients with uveal melanoma with hepatic metastasis is extremely poor, and the overall survival is generally short: less than 1 year in most cases. Immunoembolization seems to be safe, easy to administer, and potentially effective. The results obtained in the study are encouraging; however, further clinical and basic research is needed to optimize and improve the efficacy of immuno- embolization.

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