Emerging neo adjuvants for harnessing therapeutic potential of M1 tumor associated macrophages (TAM) against solid tumors: Enusage of plasticity
Vinod Nadella, Manoj Garg, Sonia Kapoor, Tushar Singh Barwal, Aklank Jain, Hridayesh Prakash
Abstract
Macrophages are a major component of the tumor microenvironment (TME) of most tumors. They are characterized by a high degree of functional plasticity which enable these cells to both promote and eliminate established tumors. Under the influence of immunosuppressive TME, tumor infiltrating iNOS+ and CD11b+ M-1 effector macrophages get polarized towards tumor associated macrophages (TAM) which are tropic to variety of tumors. Increased infiltration and density of TAM is associated with tumor progression and poor prognosis in the plethora of tumors due to their angiogenetic and tissue re-modelling nature. Importantly, TAMs are also responsible for developing endothelium anergy, a major physical barrier for majority of cancer directed immune/chemotherapies. Therefore, functional retuning/re-educating TAM to M-1 phenotypic macrophages is paramount for effective immunotherapy against established tumors. In this review, we discuss and provide comprehensive update on TAM-targeted approaches for enhancing immunity against various solid tumors.