Tumor-associated macrophages: function, phenotype, and link to prognosis in human lung cancer

Abstract

Macrophages are the dominant leukocyte population found in the tumor microenvironment. Accumulating evidence suggests that these tumor-associated macrophages (TAMs) actively promote all aspects of tumor initiation, growth, and development. However, TAMs are not a single uniform population; instead, they are composed of multiple distinct pro- and anti-tumoral subpopulations with overlapping features depending on a variety of external factors. Defining and differentiating these subsets remains a challenging work-in-progress. These difficulties are apparent in prognostic studies in lung cancer that initially demonstrated conflicting evidence regarding the significance of TAMs but which have more recently clarified and confirmed the clinical importance of these subsets through improved phenotypic capabilities. Thus, these cells represent potential targets for cancer therapeutic initiatives through translational approaches. In this review, we summarize the current understanding of how the tumor microenvironment takes advantage of macrophage plasticity to mold an immunosuppressive population, the phenotypic heterogeneity of TAMs, and their link to prognosis in human lung cancer.

Keywords: Myeloid cells; lung cancer; phenotype; prognosis; tumor microenvironment; tumor-associated macrophages.

Figure 1

The differentiation pathways of classically-activated M1 macrophages and alternatively-activated M2 macrophages [9].

Figure 2

The various pro-tumoral effector functions of TAMs [3].

Figure 3

TAM phenotypes according to pro-tumoral function [15].