Immunomodulatory effect of imiquimod through ccl22 produced by tumor-associated macrophages in B16F10 melanomas

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3461-3471
Number of pages11
JournalAnticancer research
Volume37
Issue number7
DOIs
Publication statusPublished - 2017 Jul

Keywords

  • Imiquimod
  • Melanoma
  • Regulatory T cells
  • Splenic CD11b+ cells
  • Tumor-associated macrophages

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Immunomodulatory effect of imiquimod through ccl22 produced by tumor-associated macrophages in B16F10 melanomas'. Together they form a unique fingerprint.

Cite this