Abstract
Tumor-associated macrophages (TAMs) promote tumor proliferation, invasion, angiogenesis, stemness, therapeutic resistance, and immune tolerance in a protein-dependent manner. Therefore, the traditional target paradigms are often insufficient to exterminate tumor cells. These pro-tumoral functions are mediated by the subsets of macrophages that exhibit canonical protein markers, while simultaneously having unique transcriptional features, which makes the proteins expressed on TAMs promising targets during anti-tumor therapy. Herein, TAM-associated protein-dependent target strategies were developed with the aim of either reducing the numbers of TAMs or inhibiting the pro-tumoral functions of TAMs. Furthermore, the recent advances in TAMs associated with tumor metabolism and immunity were extensively exploited to repolarize these TAMs to become anti-tumor elements and reverse the immunosuppressive tumor microenvironment. In this review, we systematically summarize these current studies to fully illustrate the TAM-associated protein targets and their inhibitors, and we highlight the potential clinical applications of targeting the crosstalk among TAMs, tumor cells, and immune cells in anti-tumor therapy.
Highlights
Received: 5 December 2021Tumor-associated macrophages (TAMs), as an integral cellular component in the tumor microenvironment (TME), promote the process involved in tumor progression, including proliferation, infiltration, angiogenesis, metastasis, stemness, immune escape, and therapeutic resistance [1]
We found that the expression of IL-1β in periodontal inflammation tissue was positively correlated with the production of both C motif chemokine ligand 2 (CCL2) and CCL5 in BC, and performing anakinra, an IL-1β inhibitor, could reduce myeloid-derived suppressor cell (MDSC) recruitment [27]
TAMs could engage in crosstalk with multiple immune cells, including CD8+ T cells, B cells, Tregs, dendritic cells (DCs), and natural killer (NK) cells, in a protein- and/or signaling-pathway-dependent manner (Figure 3)
Summary
Tumor-associated macrophages (TAMs), as an integral cellular component in the tumor microenvironment (TME), promote the process involved in tumor progression, including proliferation, infiltration, angiogenesis, metastasis, stemness, immune escape, and therapeutic resistance [1]. Since the receptors in TAMs are less likely to undergo mutation, targeting their receptors would be a promising therapeutic approach for anti-tumor therapy To support this notion, recently, in preclinical models, several special antibodies targeting their receptors were used against TAMs, including ch14.18, duvelisib (IPI-145), and ipilimumab, which were developed in neuroblastoma, T-cell lymphoma, and melanoma, respectively [5–7]. CD8+ T cells to attenuate the anti-tumor immune response [10] These findings are promising, the many obstacles of targeting proteins in TAMs need to be further explored. In this review, we systematically summarize the therapeutic approaches for targeting proteins in TAMs with regard to recruitment, polarization, crosstalk with tumor cells, and immune responses, highlighting potential strategies for targeting proteins in TAMs for anti-cancer treatment
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