New Mechanisms of Tumor-Associated Macrophages on Promoting Tumor Progression: Recent Research Advances and Potential Targets for Tumor Immunotherapy

Abstract

The majority of basic and clinical studies have shown a protumor function of tumor-associated macrophages (TAMs), which represent a large proportion of matrix cells. TAMs promote tumorigenesis, and their number is related to the malignancy degree and poor prognosis of many kinds of tumors. Macrophage plasticity makes it possible to change the tumor microenvironment and remodel antitumor immunity during cancer immunotherapy. Increasing numbers of studies have revealed the effects of TAMs on the tumor microenvironment, for example, via promotion of tumor growth and tumorigenesis and through an increase in the number of cancer stem cells or via facilitation of angiogenesis, lymphangiogenesis, and metastasis. Investigators also proposed tumor-immunological treatments targeting TAMs by inhibiting TAM recruitment and differentiation, by regulating TAM polarization, and by blocking factors and pathways associated with the protumor function of TAMs. This comprehensive review presents recent research on TAMs in relation to prediction of poor outcomes, remodeling of the tumor immune microenvironment, and immunological targeted therapies.

Coagulation and fibrinolysis in gastric cancer

“…In particular, monocytes are considered a major source of the so‐called blood‐borne TF circulating in the blood, their TF production is triggered by IL‐1β and TNF directly secreted by tumor cells. Apart from monocytes and platelets, other potential sources of blood TF include endothelial cells, granulocytes, and MPs produced by these cells, as well as macrophages, which are known to provide a suitable microenvironment for tumor invasion and progression and to contribute to the metastasis of tumor cells …”

M2‐polarized tumor‐associated macrophages promote epithelial‐mesenchymal transition via activation of the AKT3/PRAS40 signaling pathway in intrahepatic cholangiocarcinoma

“…In skin carcinoma, GM‐CSF modulated the tumor stroma, thus induced alterations in the microenvironment that facilitated tumor progression . TNF‐α derived from TAMs activates transcription of EMT‐associated transcription factors, resulting in decreased E‐cadherin expression in tumor cells . ICAM‐1 is a transmembrane protein typically expressed on epithelial cells and endothelial cells.…”

Progress on Modulating Tumor‐Associated Macrophages with Biomaterials

“…Despite the phenotypic plasticity and diversity in the tumor microenvironment, TAMs often exhibit an “M2‐like” phenotype, displaying characteristic markers such as the hemoglobin scavenger receptor (CD163) and mannose receptor (CD206). Furthermore, these cells play an anti‐inflammatory role, inducing immune suppression and promoting tumor progression through a range of mechanisms including producing immunosuppressive cytokines, suppressing cytotoxic T cell activity while promoting regulatory T cells, and inhibiting B cell signaling ( Figure ) . TAMs further potentiate tumor progression by promoting tumor cell proliferation, angiogenesis, and invasion by releasing growth factors and enzymes that digest the extracellular matrix and basement membrane.…”