Role of tumour-associated macrophages in oral squamous cells carcinoma progression: an update on current knowledge

Abstract

BackgroundOral squamous cell carcinoma (OSCC) accounts over 90% of malignant neoplasms of the oral cavity. This pathological entity is associated to a high mortality rate that has remained unchanged over the past decades. Tumour-associated macrophages (TAMs) are believed to have potential involvement in OSCC progression. However, the molecular networks involved in communication between stroma and cancer cells have not yet been fully elucidated.Main bodyThe role of M2 polarized cells in oral carcinogenesis is supported by a correlation between TAMs accumulation into OSCC stroma and poor clinical outcome. Signalling pathways such as the NF-κB and cytokines released in the tumour microenvironment promote a bidirectional cross-talk between M2 and OSCC cells. These interactions consequently result in an increased proliferation of malignant cells and enhances aggressiveness, thus reducing patients’ survival time.ConclusionsHere, we present a comprehensive review of the role of interleukin (IL)-1, IL-4, IL-6, IL-8, IL-10 and the receptor tyrosine kinase Axl in macrophage polarization to an M2 phenotype and OSCC progression. Understanding the molecular basis of oral carcinogenesis and metastatic spread of OSCC would promote the development of targeted treatment contributing to a more favourable prognosis.

Young and elderly oral squamous cell carcinoma patients present similar angiogenic profile and predominance of M2 macrophages: Comparative immunohistochemical study

“…Tumor‐associated macrophages (TAMs) appear to play an important role in the OSCC pathogenesis . In fact, macrophages have a great plasticity and innumerable functions in the innate immune response .…”

“…In fact, macrophages have a great plasticity and innumerable functions in the innate immune response . TAMs are recognized under 2 polarizations: M1 macrophages with proinflammatory and antitumor profile, and M2 macrophages exhibiting anti‐inflammatory, protumor, and proangiogenic properties . In OSCC, the macrophage polarization was assessed through CD68; CD163; CD11c; CD11b; MRC1; CD204; CD80; and CD206 immunomarkers.…”

Gas6 protein induces invasion and reduces inflammatory cytokines in oral squamous cell carcinoma

“…Gas6 and AXL were shown to be involved in the regulation of cytokines and the invasiveness of OSCC. During activation, Gas6 binds to AXL and achieves biological function by activating the AKT pathway and by modulating epithelial‐mesenchymal transition, which promotes cell invasion . The relationship between inflammation and the regulation of OSCC invasion by Gas6/AXL requires further investigation.…”

Tanshinones in management of oral submucous fibrosis and oral squamous cell carcinoma

“…[3] Every year, OSCC is estimated to occur in more than 400,000 people worldwide. [4] Every year, 120,000 deaths occur due to OSCC. [3] Currently, there are several modes of management of OSCC and OSMF, depending upon the stage of the disease and several other factors.…”

“…The 5-year survival of OSCC patients still remains to be 50%. [4] Currently, there is much interest in exploring compounds extracted from natural products to treat OSCC and OSMF. Natural products have added advantage of having lesser or no side effects compared with currently used chemotherapy agents and radiotherapy mode of management.…”