All trans-retinoic acid abrogates the pro-tumorigenic phenotype of prostate cancer tumor-associated macrophages

• Prostate cancer cell-derived factors induce a pro-tumoral phenotype in macrophages.
• ATRA inhibits the pro-tumoral macrophage phenotype by blocking NFkB activation.
• ATRA does not diminish the phosphorylation of ERK in tumor-associated macrophages.

Tumor-associated macrophages (TAMs) are a prominent cell type of the tumor stroma and stimulate malignant cell growth, survival and metastasis. The present manuscript demonstrates that prostate cancer cell-derived factors induce a pro-tumoral TAM-like phenotype characterized by increased proliferation and increased expression of pro-angiogenic, immunosuppressive and pro-metastatic factors. These effects were abrogated by all trans-retinoic acid (ATRA), a clinically available molecule with known immune-modulating properties. Furthermore, ATRA inhibited the cancer cell-stimulated proliferation of the pro-tumoral macrophages and restored their cytotoxic capacity towards prostate cancer cells. These findings suggest the use of ATRA as an immunomodulating agent to block the activity of prostate cancer TAMs.