Macrophage’s role in solid tumors: two edges of a sword

Abstract

The tumor microenvironment is overwhelmingly dictated by macrophages, intimately affiliated with tumors, exercising pivotal roles in multiple processes, including angiogenesis, extracellular matrix reconfiguration, cellular proliferation, metastasis, and immunosuppression. They further exhibit resilience to chemotherapy and immunotherapy via meticulous checkpoint blockades. When appropriately stimulated, macrophages can morph into a potent bidirectional component of the immune system, engulfing malignant cells and annihilating them with cytotoxic substances, thus rendering them intriguing candidates for therapeutic targets. As myelomonocytic cells relentlessly amass within tumor tissues, macrophages rise as prime contenders for cell therapy upon the development of chimeric antigen receptor effector cells. Given the significant incidence of macrophage infiltration correlated with an unfavorable prognosis and heightened resistance to chemotherapy in solid tumors, we delve into the intricate role of macrophages in cancer propagation and their promising potential in confronting four formidable cancer variants—namely, melanoma, colon, glioma, and breast cancers.

Nanomedicine as a multimodal therapeutic paradigm against cancer: on the way forward in advancing precision therapy

“…87 The cellular microenvironment involves bone marrow-derived antigen-presenting cells (APCs, e.g., DCs), tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and cancer stem cells (CSCs), which can self-renew and promote tumor growth, and therapy resistance. 88,89 Whereas the physiological microenvironment consists of chronic/cyclic hypoxia (due to abnormal blood vessels and uncontrolled tumor cell proliferation leading to altered oxygen tension within the tumor vasculature), an acidic environment (due to insufficient blood supply and tumor cells glycolytic metabolism), and an alteration in various metabolic pathways (such as amino acid metabolism, increase in glucose uptake/lactate fermentation due to activated mitochondria under aerobic environment) etc. 90,91 Within the TME, the co-existence and dynamic communication of tumor cells with the extracellular matrix (ECM), stromal cells recruited from the bone marrow/surrounding tissues (e.g., fibroblasts), immune cells (e.g., macrophages, resident microglia), lymphatic and vascular endothelial cells, pericytes, inflammatory mediators, such as soluble factors (e.g., cytokines, chemokines), and ECM-degrading enzymes (e.g., matrix metalloproteases [MMPs]) etc.…”

Effectiveness of Rhenium(I)-diselenoether Low Doses in a Triple-negative Breast Cancer Chicken Embryo Model

“…Tumor-associated macrophages (TAMs) may have pro-or anti-inflammatory properties (25) and their role is primordial in the cancer development (26). The significant incidence of macrophage infiltration is commonly correlated with an unfavorable prognosis, but it could be more relevant to characterize the type of macrophages.…”

Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy

“…These processes have been linked to the development of therapeutic resistance to chemotherapy and radiotherapy in colorectal, pancreatic, or ovarian cancers [ 4 , 52 , 89 – 92 ]. However, this immune cell subtype can also have beneficial effects in cancer therapy, as it has been observed that they can induce an anti-inflammatory response and promote tissue repair during cancer treatment [ 93 , 94 ].…”

“…As the focus on understanding the pivotal role of TAMs in tumour development intensifies, it has become increasingly clear that TAMs exert a wide range of functions in shaping the TME in favour of tumour initiation and progression [ 93 ]. This underscores the significance of TAMs as pivotal participants throughout the entire spectrum of this pathology, involving various components of the immune system.…”