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

// Xiang Zheng 1 , Kati Turkowski 1 , Javier Mora 2 , Bernhard Brune 2 , Werner Seeger 1, 3 , Andreas Weigert 2 and Rajkumar Savai 1, 3 1 Max Planck Institute for Heart and Lung Research, Department of Lung Development and Remodeling, Member of the German Center for Lung Research (DZL), Bad Nauheim, Germany 2 Institute of Biochemistry I, Goethe-University Frankfurt, Frankfurt, Germany 3 Department of Internal Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the DZL, Justus Liebig University, Giessen, Germany Correspondence to: Rajkumar Savai, email: rajkumar.savai@mpi-bn.mpg.de Andreas Weigert, email: weigert@biochem.uni-frankfurt.de Keywords: tumor microenvironment, macrophages, repolarization, cancer progression, metastasis Received: October 15, 2016     Accepted: March 22, 2017     Published: April 12, 2017 ABSTRACT 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.