Targeting tumor‑associated macrophages in the tumor microenvironment (Review)

Abstract

Tumor-associated macrophages (TAMs) are the most abundant population type of tumor-infiltrating immune cells found in the tumor microenvironment (TME), and are evolutionarily associated with microvessel density in tumor tissues. TAMs can be broadly divided into M1-like and M2-like TAMs, which demonstrate antitumor and pro-tumor activity in the TME, respectively. Studies have indicated that: i) The predominate presence of M2-like TAMs in the TME can result in tumor immunosuppression and chemoresistance; ii) the ratio of M1-like to M2-like TAMs in the TME is positively correlated with better long-term prognosis of patients with cancer; iii) epigenetic silencing, preventing the secretion of M1-like TAM-associated molecules, is an important immune evasion mechanism during tumor progression; and iv) the transformation from M2-like to M1-like TAMs following exposure to specific conditions can result in tumor regression. The present study discusses the molecular events underlying the recruitment of macrophages and their polarization into M1-like or M2-like TAMs, and their differential roles in angiogenesis, angiostasis, invasion, metastasis and immune activity in the TME. This insight may inform the improved design of TAM-targeted cancer immunotherapy. Some of these therapeutic strategies show promising effects; however, challenges remain.

Bioinformatic analyses and experimental validation of the role of m6A RNA methylation regulators in progression and prognosis of adrenocortical carcinoma

“…The increased proportion of resting NK cells indicates the suppression of the anti-tumor cellular immunity. Macrophages are polarized into M1 and M2 types by different inducers [ 46 ]. M1 macrophages induced by interferon (IFN)-γ and TNF-α, possessed promote-inflammatory and cytotoxic antitumor abilities [ 47 ].…”

“…M1 macrophages induced by interferon (IFN)-γ and TNF-α, possessed promote-inflammatory and cytotoxic antitumor abilities [ 47 ]. However, M2 macrophages were commonly responsible for tumor immunosuppression [ 46 ]. Therefore, the decreased of Macrophages M1 was also disadvantageous to anti-tumor immunity.…”

Survivin drives tumor-associated macrophage reprogramming: a novel mechanism with potential impact for obesity

“…In addition to tumor cells, the tumor microenvironment contains a complex network of immune cells, adipocytes, myofibroblasts and mesenchymal stem cells, including ASCs [13]. Some of these cells secrete chemokines (e.g., CCL2/MCP-1), cytokines (e.g., IL-4, IL-13) and growth factors (e.g., VEGF, CSF1/M-CSF and CSF2/GM-CSF) that trigger the recruitment of monocytes, and can promote cancer progression through the activation of tumor-associated macrophages (TAMs) [14,15]. TAMs comprise 50-80% of the tumor mass, and their presence often correlates with a poor prognosis in most cancers [16][17][18].…”

T‐cell immunoglobulin and ITIM domain, as a potential immune checkpoint target for immunotherapy of colorectal cancer

“…Second, TIGIT expressing Tregs suppress Th1, Th17, and CD8+ T cells; however, they do not inhibit Th2 function. IL‐4 made by Th2 lymphocytes stimulates both B cells and the differentiation of the TAMs into TAM2, which secrete TGF‐β, IL‐10, and arginase‐1, to suppress immune responses and allow tumor cells to evade immune surveillance mechanisms 63,95–97 . Besides, TIGIT can affect nearby APCs or tumor cells by binding to CD155/CD112/CD113 and can also cause the generation of the tolerogenic phenotype of APCs like DCs, which secrets more IL‐10 than IL‐12 23 …”