Exosome-mediated communication between tumor cells and tumor-associated macrophages: implications for tumor microenvironment

Abstract

Exosomes are extracellular vesicles released from numerous types of cells that are involved in multiple tumors development. Exosomes contribute to the modulation of tumor microenvironment (TME) through intercellular communication. As essential immune stromal cells in the TME, tumor-associated macrophages (TAMs) participate in tumor development by mediating angiogenesis, metastasis, chemoresistance, and immune escape. Due to communication with multiple cells in the TME, they exhibit plasticity and heterogeneity during the progress of polarization from monocytes to macrophages. Previous studies suggest that targeting TAMs is a promising therapeutic strategy; however, the detailed mechanism by which TAMs regulate tumor development still remains unclear. In this review, we provide an overview of the roles of exosomes as messengers in the communication between tumor cells and polarization of TAMs; we also describe the effects of their interaction on tumor development. Finally, we comprehensively discussed the potential application of exosomes as the promising tumor immunotherapy strategy.

Autophagy in major human diseases

“…Extracellular release of KRAS G12D by cancer cells succumbing to autophagy‐dependent ferroptosis is essential for pancreatic tumor‐associated macrophages (TAM) to switch to an “M2‐like” immunosuppressive phenotype (Dai et al , 2020 ). Importantly, M2 TAMs have been linked to tumor progression, metastases (Han et al , 2021 ), and resistance to conventional chemotherapeutics (Larionova et al , 2019 ) in multiple tumors. Consistent with this finding, chloroquine and its derivative hydroxychloroquine improve TAM‐mediated anticancer immune response by promoting the establishment of an “M1‐like” phenotype (Chen et al , 2018a ; Sharma et al , 2020 ).…”

Cancer derived exosomes induce macrophages immunosuppressive polarization to promote bladder cancer progression

“…Emerging evidence has suggested that the communication between tumor cells and macrophages plays a key role in mediating TAM polarization [ 14 , 15 ]. Signals originated from tumor cells such as transforming growth factor beta (TGF-β), could promote differentiation of non-activated macrophages into a TAM-like immunosuppressive phenotype characterized as increased anti-inflammatory cytokine and decreased pro-inflammatory cytokine expression [ 11 , 16 ].…”

Immune Cell-Derived Extracellular Vesicles – New Strategies in Cancer Immunotherapy

“…Macrophage-derived EVs have multiple functions depending on various phenotypes of parental cells. Both endogenous and exogenous stimulatory factors influence the secretion of macrophage-derived EVs ( 62 ). Lysosomes can fuse with multivesicular bodies to determine their trafficking pathway.…”