Roles of tumor-associated macrophages in tumor progression: implications on therapeutic strategies

Abstract

Macrophages are heterogeneous cells that present as different functional phenotypes due to their plasticity. They can be classified into two categories, namely M1- and M2-like macrophages, which are involved in processes as diverse as anti-tumor activity and immunosuppressive tumor promotion. Tumor-associated macrophages (TAMs) are defined as being of an M2-type and are considered as the active component in tumor microenvironment. TAMs are involved in multiple processes of tumor progression through the expression of cytokines, chemokines, growth factors, protein hydrolases and more, which lead to enhance tumor cell proliferation, angiogenesis, and immunosuppression, which in turn supports invasion and metastasis. It is assumed that the abundance of TAMs in major solid tumors is correlated to a negative patient prognosis. Because of the currently available data of the TAMs’ role in tumor development, these cells have emerged as a promising target for novel cancer treatment strategies. In this paper, we will briefly describe the origins and types of TAMs and will try to comprehensively show how TAMs contribute to tumorigenesis and disease progression. Finally, we will present the main TAM-based therapeutic strategies currently available.

Targeting PD-1/PD-L1 pathway in myelodysplastic syndromes and acute myeloid leukemia

“…Physiologically, PD-1 is expressed on activated T cells, Tregs and B cells. PD-1 prevents immune overactivation by binding to its receptor PD-L1/PD-L2 found mainly on macrophages and dendritic cells (DCs) [ 33 – 37 ]. Following binding to PD-L1, the intracellular tyrosine residue of PD-1 is phosphorylated, followed by subsequent SHP-1 and SHP-2 recruitment, which disrupts a series of downstream molecules in TCR signaling, e.g., PI3K/AKT, RAS-ERK1/2 and PKCδ signaling.…”

MicroRNA-200c Attenuates the Tumor-Infiltrating Capacity of Macrophages

“…Since high TAM counts correlate with tumor progression and poor survival [8,9], our finding that miR-200c attenuates MΦ recruitment into tumors suggests an anti-tumorigenic function of miR-200c in the TME. Similarly, ectopic miR-200c expression was previously shown to support an anti-tumoral T-cell phenotype in adoptive T-cell therapy models [79].…”

“…In fact, in BC, TAM may account for up to 50% of the tumor mass [5][6][7]. High numbers of infiltrating TAM further correlate with poor survival in most solid tumors [8,9]. While macrophages (MΦ) are initially a part of the anti-tumor response, their polarization changes to a pro-tumoral M2-like phenotype with anti-inflammatory and immunosuppressive properties within the TME [10,11].…”

Correction to: Roles of tumor-associated macrophages in tumor progression: implications on therapeutic strategies

“…Following publication of the original article [ 1 ], the author reported error in first author name. The first author name was misspelling in the submitted version and published as Shangli Zhu.…”