Macrophages directed approaches are paramount for effective cancer immunotherapies

Abstract

Macrophages are double edge sword component of immunity and display phenotypical and functional plasticity which enable them to both promote and eliminate established tumors. Under the influence of immunosuppressive tumor microenvironment, tumor infiltrating iNOS+ and CD11b+ M-1 regulatory macrophages get polarized to Tumor associated macrophages (TAM) which are Ym-1 and Arginase+ iNOS-(M-2) and tropic to variety of tumors. Increased density of TAM in the variety of tumors has been correlated with poor prognosis which is due to their influence on angiogenesis and tissue re-modelling by which TAM support tumorigenesis as well metastasis. Apart from this, TAMs are also responsible for the maintenance of tumor microenvironment by their virtue of inducing endothelium anergy, which actually represent physical barrier for majority of cancer directed immune / chemotherapies. Therefore functional retuning of TAM to an M-1 phenotype is paramount for effective immunotherapy against established tumors which could be afforded by total body gamma irradiation in neoadjuvant settings or adoptive transfer of iNOS+ macrophages. In this review, we will discuss both existing as well future cancer directed immuno / adjuvant therapies targetting immunosuppresive tumor microenviorment particularly tumor-associated macrophages (TAM) for enhancing immunty against solid tumors (adenocarcinoma).