Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment

Abstract

During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy.

PLD4 promotes M1 macrophages to perform antitumor effects in colon cancer cells

“…M1 macrophages stimulated cell-mediated responses via secreting pro-inflammatory cytokines such as IL-1, IL-6, IL-12, IL-23 and TNf-α. furthermore, the M1 macrophages served as a critical cellular component involved in the inflammatory response and antitumor function (12). Conversely, the M2 macrophages exerted anti-inflammatory and pro-tumorigenic activities through the production of anti-inflammatory cytokines (IL-10 and TGF-β) and high levels of decoys that antagonized IL-1, such as IL1RII and IL-1 receptor antagonist (10,13).…”

Immune Checkpoint Inhibitors in Gynecological Cancers: Update of Literature and Perspectives of Clinical Research

“…Heeren et al (106) assessed PD-L1 expression in tumor specimens from two cohorts of CC patients: primary tumor samples from cohort I (squamous cell carcinoma (SCC), n=156 and adenocarcinoma (AD), n=49) and primary and paired metastatic tumor samples from cohort II (SCC, n=96 and AD, n=31). PD-L1 positivity was observed in >5% of the tumor cells in 54% of SCCs and in 14% of ADs (p<0.001), PD-L1-positive TAMs were present in 53% of the former and 12% of the latter (p<0.001) displaying an M2-like phenotype characterized by protumorigenic properties (107). DFS and DSS were significantly poorer in SCC patients with diffuse PD-L1 expression than in those with marginal PD-L1 expression in primary tumors (p=0.022 and p=0.046, respectively).…”

Inhibition Effects of Lamellarin D on Human Leukemia K562 Cell Proliferation and Underlying Mechanisms

“…Inflammatory cells play important roles in tumor metastasis; IL-6, IL-1β, IL-8 and other inflammatory cytokines stimulate tumor cell proliferation (Chanmee et al, 2014;Peppicelli et al, 2014;Voronov E et al, 2014;El-Kadre et al, 2013). TGF-β can induce the expression of multiple transcription factors and upregulate tumor-related gene expression, subsequently promoting tumorigenesis (Taylor et al, 2013;Li et al, 2014).…”