Novel insights in the regulation and function of macrophages in the tumor microenvironment.

PURPOSE OF REVIEW: Tumors contain not only cancer cells but also nontransformed types of cells, the stromal cells. A bidirectional interplay exists between transformed and nontransformed cells leading to tumor progression and metastasis. Tumor-associated macrophages (TAMs) are the most abundant tumor-infiltrating leukocytes characterized by a high heterogeneity and plasticity. TAMs exhibit strong protumoral activities and are related to bad prognosis and worse overall survival in various cancer types.

RECENT FINDINGS: Recent progress has delineated the existence of distinct TAM subsets in primary tumors and metastatic sites regulated by diverse mechanisms and triggering strong protumoral functions such as immunossuppression, angiogenesis, metastasis and resistance to current therapies.

SUMMARY: Delineating the regulatory pathways governing TAM heterogeneity and activation could present a novel frontier in cancer therapy. TAM targeting/repolarization is considered as a promising novel therapeutic modality in combination with standard-of-care therapies or immuno checkpoint blockers.