Redirecting tumor-associated macrophages to become tumoricidal effectors as a novel strategy for cancer therapy

Cancer research in recent decades has highlighted the potential influence of the tumor microenvironment on the progression and metastasis of most known cancer types. Within the established microenvironment, tumor-associated macrophages (TAMs) are one of the most abundant and crucial non-neoplastic cell types. The polarization of macrophages into tumor-suppressive M1 or tumor-promoting M2 types is a fundamental event in the establishment of the tumor microenvironment. Although ample evidence indicates that TAMs are primarily M2 polarized, the mechanisms responsible for the regulation and maintenance of M1 and M2 polarization imbalance remain unclear. The manipulation of this critical axis through three main approaches may provide new strategies for cancer therapy — (I) specific interference with M2-like TAM survival or inhibiting their signaling cascades, (II) repression of macrophage recruitment to tumors, and (III) repolarization of tumor-promoting M2-like TAMs to a tumoricidal M1-like phenotype. This review summarizes current strategies for cancer intervention via manipulation of macrophage polarization, with particular focus on composition of the tumor microenvironment and its influence on cancer progression and metastasis. It is clear that additional fundamental and preclinical research is required to confirm the efficacy and practicality of this novel and promising strategy for treating cancer.