Tumor associated macrophages (TAMs) target for cancer treatment: new promising route in cancer immunotherapy

Introduction: Tumor-associated macrophages (TAM) especially M2 types play a critical role in cancer invasion and metastasis. Cancer- and host cell-derived signals generally drive the functions of TAMs towards an M2-like polarized, tumor-propelling mode; however, when appropriately re-educated. TAMs also have the potential to elicit tumor destructive reactions. Thus, targeting TAMs would impede the implicated mechanisms and enhance survival rate of patients.Methods: We utilized PubMed database and we used cancer therapy, inflammatory microenvironment, macrophages, macrophage recruitment, chemokines, and tumour associated macrophage as keywords. Finally, we included 20 literatures which related to our topic. Results: Experimental investigations indicate that TAMs contribute to drug-resistance and radio-protective effects, and clinical evidence shows that an elevated number of TAMs and their M2 profile are correlated with therapy failure and poor prognosis in cancer patients. Several studies on TAM-targeted strategies have led to significant progress and some pilot works have achieved encouraging results. Among these, connections between some anti-tumour drugs such as inhibitors of CCL2/CCR2 (e.g. Yondeli and RS102895), inhibitors of M-CSF/M-CSFR (e.g. anti-M-CSF mAb,JNJ-28312141 and GW2580), agonists of STAT1 (e.g. interferon), agonists of other M1 pathways (e.g. SHIP), and Inhibitors of STAT6 and their influence on TAMs have been suggested. Strategies of targeting TAMs are grouped into four categories based on the proposed mechanisms: (i) inhibiting macrophage recruitment; (ii) suppressing TAM survival; (iii) enhancing M1-like tumoricidal activity of TAMs; (iv) blocking M2-like tumour-promoting activity of TAMs.Conclusion: In sum, targeting TAMs in different types of cancer would be promising and providing desirable results in cancer treatment and open a novel effective cancer treatment strategy in the future.

Keywords:

cancer therapy , recruitment , survival , Chemokines , Inflammation , Macrophages , tumour associated macrophage