Instruction of myeloid cells by the tumor microenvironment: Open questions on the dynamics and plasticity of different tumor-associated myeloid cell populations

Abstract

The versatility and plasticity of myeloid cell polarization/differentiation has turned out to be crucial in health and disease, and has become the subject of intense investigation during the last years. On one hand, myeloid cells provide a critical contribution to tissue homeostasis and repair. On the other hand, myeloid cells not only play an important role as first line defense against pathogens but also they are involved in a broad array of inflammation-related diseases such as cancer. Recent studies show that macrophages can exist in different activation states within the same tumor, underlining their plasticity and heterogeneity. In this review, we will discuss recent evidence on how the tumor microenvironment, as it evolves, shapes the recruitment, function, polarization and differentiation of the myeloid cell compartment, leading to the selection of myeloid cells with immunosuppressive and angiogenic functions that facilitate tumor progression and dissemination.

Newly Recruited CD11b+, GR-1+, Ly6Chigh Myeloid Cells Augment Tumor-Associated Immunosuppression Immediately following the Therapeutic Administration of Oncolytic Reovirus

“…In mice, MDSCs were originally defined as cells expressing CD11b (aM-integrin) and Gr-1 markers, whereas in humans these cells were mainly defined as CD11b , CD33 + cells. However, it is now clear that MDSCs represent a heterogeneous population of cells that consists of progenitor as well as immature myeloid cells (IMCs) (22,23). These subpopulations of MDSCs are shown to have differential biological roles and require further phenotypical characterization to enable precise therapeutic targeting.…”

Clinicopathological correlation of tumor-associated macrophages in Ewing sarcoma

“…Due to the heterogeneity of the macrophage population, their role in the tumor microenvironment is very complex [22][23][24][25][26][27] . TAMs can develop a continuum of polarization states with the tumor-suppressing M1 macrophages lying on one end and the tumor-promoting M2 macrophages on the other.…”

“…TAMs can develop a continuum of polarization states with the tumor-suppressing M1 macrophages lying on one end and the tumor-promoting M2 macrophages on the other. The proportional representation and localization of the different phenotypes of TAMs in the tumor tissue determine the overall influence of the macrophage population in a given neoplasia 26,27 . For the patient, the effect of TAMs can therefore be either beneficial or adverse 29,30 .…”

“…In the past, M2 macrophages were almost exclusively considered to be responsible for tumor promoting effects but accumulating evidence have suggested that it was an oversimplification. TAMs are composed of multiple macrophage populations with overlapping features that depend on the mix of signals in their direct microenvironment 26,27 . Currently, the role of TAMs in ES is not fully understood.…”

Alpha1-antitrypsin, an endogenous immunoregulatory molecule: distinction between local and systemic effects on tumor immunology

“…Yet a tumor mass is not absent model. Thus, being that hypoxic conditions lead to stabilization of hypoxia-inducible factor-1α (HIF-1α) and HIF-2α [86] and that AAT is induced by hypoxia, one must take into account the tight association between local conditions and AAT expression in the detrimental junction of TAM profile acquisition.…”