The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy

Abstract

Macrophages have a leading position in the tumor microenvironment (TME) which paves the way to carcinogenesis. Initially, monocytes and macrophages are recruited to the sites where the tumor develops. Under the guidance of different microenvironmental signals, macrophages would polarize into two functional phenotypes, named as classically activated macrophages (M1) and alternatively activated macrophages (M2). Contrary to the anti-tumor effect of M1, M2 exerts anti-inflammatory and tumorigenic characters. In progressive tumor, M2 tumor-associated macrophages (TAMs) are in the majority, being vital regulators reacting upon TME. This review elaborates on the role of TAMs in tumor progression. Furthermore, prospective macrophage-focused therapeutic strategies, including drugs not only in clinical trials but also at primary research stages, are summarized followed by a discussion about their clinical application values. Nanoparticulate systems with efficient drug delivery and improved antitumor effect are also summed up in this article.

Keywords: Combined therapy; Extracellular vesicles; Immunotherapy; Nano-drug; Targeted drug delivery; Tumor microenvironment; Tumor treatment; Tumor-associated macrophages.

Graphical abstract

Figure 1

Schematic Illustration of lipid-coated calcium zoledronate nanoparticles (CaZol@) containing conjugated mannose targeting TAMs and inducing their apoptosis. Reprinted with permission from Ref. 127. Copyright © 2019 American Chemical Society.

Figure 2

Schematic illustration to demonstrate the progress of releasing the small peptide T4 from a dual-responsive amphiphilic peptide and targeting to both macrophage and endothelial cell, which consequently inhibit tumor angiogenesis. Reprinted with permission from Ref. 153. Copyright © 2019 American Chemical Society.

Figure 3

Schematic illustration of CINPs for tumorigenesis inhibition by inducting macrophage repolarization and synergizing photothermal therapy. Reprinted with permission from Ref. 175. Copyright © 2019 American Chemical Society.