Targeting the depletion of M2 macrophages: implication in cancer immunotherapy

We have witnessed the emergence of immunotherapy against various cancers that resulted in significant clinical responses and particularly in cancers that were resistant to chemotherapy. These milestones have ignited the development of novel strategies to boost the anti-tumor immune response for immune-suppressed tumors in the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are the most abundant cells in the TME, and their frequency correlates with poor prognosis. Hence, several approaches have been developed to target TAMs in effort to restore the anti-tumor immune response and inhibit tumor growth and metastasis. One approach discussed herein is targeting TAMs via their depletion. Several methods have been reported for TAMs depletion including micro-RNAs, transcription factors (e.g., PPARγ, KLF4, STAT3, STAT6, NF-κB), chemokines and chemokine receptors, antibodies-mediated blocking the CSF-1/CSF-1R pathway, nanotechnology, and various combination treatments. In addition, various clinical trials are currently examining the targeting of TAMs. Many of these methods also have side effects that need to be monitored and reduced. Future perspectives and directions are discussed.