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Anticancer Res. 2017 Jul;37(7):3461-3471.

Immunomodulatory Effect of Imiquimod Through CCL22 Produced by Tumor-associated Macrophages in B16F10 Melanomas.

Author information

1
Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
2
Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan tfujimura1@mac.com.

Abstract

BACKGROUND/AIM:

Tumor-associated macrophages (TAMs), together with splenic CD11b+ cells, help maintain the tumor microenvironment. The immunomodulatory compound imiquimod (IQM) stimulates innate immune cells, including macrophages, to induce antitumor effects. In order to elucidate the effects of IQM on the tumor microenvironment, we investigated the immunomodulatory effect of IQM during melanoma growth by using the B16F10 melanoma model.

MATERIALS AND METHODS:

To elucidate the immunomodulatory effects of IQM on the tumor microenvironment, we isolated CD11b+ TAMs and splenic CD11b+ cells and evaluated the immunomodulatory effects of IQM, using the B16F10 melanoma model.

RESULTS:

IQM suppressed B16F10 melanoma growth in parallel with reduction of Foxp3+ regulatory T cells (Tregs) at the tumor site, caused by the down-regulation of CCL22 production by tumor-derived and splenic CD11b+ cells. Subsequently, we investigated the antitumor or tumor-loading effects of splenic CD11b+ cells on B16F10 melanoma growth in vivo. B16F10 melanoma growth was accelerated by splenic CD11b+ cells from untreated mice, but was inhibited by splenic CD11b+ cells from IQM-treated mice. Consistent with these results, Foxp3+ Tregs were significantly decreased in tumors of mice implanted with both melanoma and splenic CD11b+ cells from topical IQM-treated mice. Furthermore, intratumoral administration of anti-CCL22 antibody inhibited B16F10 melanoma growth by decreasing Treg recruitment at the tumor site.

CONCLUSION:

Our results suggest a possible mechanism for the antitumor immune response induced by IQM through tumor-associated macrophages.

KEYWORDS:

Tumor-associated macrophages; imiquimod; melanoma; regulatory T cells; splenic CD11b+ cells

PMID:
28668835
DOI:
10.21873/anticanres.11714
[Indexed for MEDLINE]

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