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

View Article: PubMed Central - PubMed

ABSTRACT

Background: Oral 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 body: The 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.

Conclusions: Here, 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.

No MeSH data available.


Related in: MedlinePlus

Macrophages in resting state suffer microenvironmental effects coordinated by OSCC cells. Interleukin (IL)-1, IL-4, IL-6, IL-8 and IL-10 (not shown), and Gas-6 are produced by OSCC cells and promote macrophage phenotype switching to an M2 polarization state. In turn, TAMs augment the recruitment of chemotactic receptors to tumour sites, induce tumour proliferation, and favour angiogenesis and invasiveness [31, 32, 36, 40–43, 47, 48, 65, 66]
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC5382416&req=5

Fig1: Macrophages in resting state suffer microenvironmental effects coordinated by OSCC cells. Interleukin (IL)-1, IL-4, IL-6, IL-8 and IL-10 (not shown), and Gas-6 are produced by OSCC cells and promote macrophage phenotype switching to an M2 polarization state. In turn, TAMs augment the recruitment of chemotactic receptors to tumour sites, induce tumour proliferation, and favour angiogenesis and invasiveness [31, 32, 36, 40–43, 47, 48, 65, 66]

Mentions: Histopathologically, OSCC presents as fibrous connective tissue with unusual amounts of extracellular matrix rich in fibroblasts, vascular vessels, and inflammatory cells [26]. Among the local milieu of OSCC stromal spaces, rich in perlecans and inflammatory cells, monocytes or resting macrophages are differentiated into LyC16high, CD163+, CD204+, and CD68+ expressing TAMs. These cells are considered of utmost biological importance for disease progression and correlate with increased dedifferentiation in primary tumour sites [27–29]. Moreover, TAMs elicit tumour relapse and/or post-operative cervical lymph node metastasis via angiogenesis and suppression of anti-tumour immunity [9]. An increase in the number of CD163+ macrophages occurs in oral leukoplakia. However, they co-express phosphorylated STAT-1, suggesting that in premalignant lesions TAMs possess an M1 phenotype in a dominant TH1 microenvironment [30]. Polarization to an M2 TAM phenotype probably occurs gradually and early during the onset of cancer. It is suggested that several interleukins (IL-1, IL-4, IL-6, IL-8, and IL-10), and other factors, such as the receptor tyrosine kinase Axl, participate in promoting this phenomenon. In the next sections we propose a topic structured discussion of relevant findings that corroborate this theoretical assumption. Figure 1 briefly reviews the effect of interleukins on TAMs present in OSCC stroma.Fig. 1


Role of tumour-associated macrophages in oral squamous cells carcinoma progression: an update on current knowledge
Macrophages in resting state suffer microenvironmental effects coordinated by OSCC cells. Interleukin (IL)-1, IL-4, IL-6, IL-8 and IL-10 (not shown), and Gas-6 are produced by OSCC cells and promote macrophage phenotype switching to an M2 polarization state. In turn, TAMs augment the recruitment of chemotactic receptors to tumour sites, induce tumour proliferation, and favour angiogenesis and invasiveness [31, 32, 36, 40–43, 47, 48, 65, 66]
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5382416&req=5

Fig1: Macrophages in resting state suffer microenvironmental effects coordinated by OSCC cells. Interleukin (IL)-1, IL-4, IL-6, IL-8 and IL-10 (not shown), and Gas-6 are produced by OSCC cells and promote macrophage phenotype switching to an M2 polarization state. In turn, TAMs augment the recruitment of chemotactic receptors to tumour sites, induce tumour proliferation, and favour angiogenesis and invasiveness [31, 32, 36, 40–43, 47, 48, 65, 66]
Mentions: Histopathologically, OSCC presents as fibrous connective tissue with unusual amounts of extracellular matrix rich in fibroblasts, vascular vessels, and inflammatory cells [26]. Among the local milieu of OSCC stromal spaces, rich in perlecans and inflammatory cells, monocytes or resting macrophages are differentiated into LyC16high, CD163+, CD204+, and CD68+ expressing TAMs. These cells are considered of utmost biological importance for disease progression and correlate with increased dedifferentiation in primary tumour sites [27–29]. Moreover, TAMs elicit tumour relapse and/or post-operative cervical lymph node metastasis via angiogenesis and suppression of anti-tumour immunity [9]. An increase in the number of CD163+ macrophages occurs in oral leukoplakia. However, they co-express phosphorylated STAT-1, suggesting that in premalignant lesions TAMs possess an M1 phenotype in a dominant TH1 microenvironment [30]. Polarization to an M2 TAM phenotype probably occurs gradually and early during the onset of cancer. It is suggested that several interleukins (IL-1, IL-4, IL-6, IL-8, and IL-10), and other factors, such as the receptor tyrosine kinase Axl, participate in promoting this phenomenon. In the next sections we propose a topic structured discussion of relevant findings that corroborate this theoretical assumption. Figure 1 briefly reviews the effect of interleukins on TAMs present in OSCC stroma.Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

Background: Oral 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 body: The 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.

Conclusions: Here, 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.

No MeSH data available.


Related in: MedlinePlus