Review articleTumor promoting role of anti-tumor macrophages in tumor microenvironment

- TAM in tumor microenvironment promotes tumor growth, angiogenesis and metastasis.
- Polarization of TAMs to M2 phenotype is crucial in pro-tumorigenic process.
- M2 TAMs can be targeted in tumors as a promising therapeutic strategy.
- Targeting includes inhibition of M2 attraction and M1 polarization.
- Blocking their pro-tumoral functions and reprogramming M2 to M1 form are preferred.

Recent advances in tumor biology demand detailed analysis of the complex interaction of tumor cells with their adjacent microenvironment (tumor stroma) to understand the various mechanisms involved in tumor growth and metastasis. Mononuclear phagocytes or macrophages, a type of innate immune cells, defend the organism against infection and injury. On the otherhand, tumor associated macrophages (TAMs) constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype. Clinical and experimental evidences have shown that cancer tissues with high infiltration of TAMs are associated with poor patient prognosis and resistance to therapies, thus, targeting of TAMs in tumors is considered as a promising immunotherapeutic strategy. Depletion of M2 TAMs or 're-education' of them as anti-tumor effectors might contribute significantly to the search of new modalities in anti-cancer treatments. Basic questions on the factors responsible for homing of macrophages in tumors, mechanism of conversion of M1 to M2 TAMs, their functionality and, finally, the possible ways to target M2 TAMs are discussed.