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Review
. 2023 Jun 8;24(12):9874.
doi: 10.3390/ijms24129874.

The Role of IL-17 in the Pathogenesis of Oral Squamous Cell Carcinoma

Nevena Ladjevac  1   2 , Marija Milovanovic  2   3 , Andra Jevtovic  2   4 , Dragana Arsenijevic  2   5 , Bojana Stojanovic  2   6 , Milica Dimitrijevic Stojanovic  2   7 , Bojan Stojanovic  2   8 , Nebojsa Arsenijevic  2   3 , Aleksandar Arsenijevic  2   3 , Jelena Milovanovic  2   9
Affiliations
Review

The Role of IL-17 in the Pathogenesis of Oral Squamous Cell Carcinoma

Nevena Ladjevac et al. Int J Mol Sci. .

Abstract

Elucidating the inflammatory mechanisms underlying formation and progression of oral squamous cell carcinoma (OSCC) is crucial for discovering new targeted therapeutics. The proinflammatory cytokine IL-17 has proven roles in tumor formation, growth, and metastasis. The presence of IL-17 is demonstrated in both in vitro and in vivo models, and in OSCC patients, is mostly accompanied by enhanced proliferation and invasiveness of cancer cells. Here we review the known facts regarding the role of IL-17 in OSCC pathogenesis, namely the IL-17 mediated production of proinflammatory mediators that mobilize and activate myeloid cells with suppressive and proangiogenic activities and proliferative signals that directly induce proliferation of cancer cells and stem cells. The possibility of a potential IL-17 blockade in OSCC therapy is also discussed.

Keywords: inflammation; interleukin-17 (IL-17); oral squamous cell carcinoma (OSCC); therapeutic target; tumor progression.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Interleukin-17 signaling. The IL-17R mediated transcriptional and posttranscriptional changes in target cells.
Figure 2
Figure 2
The roles of IL-17 induced mediators in OSCC pathogenesis. Interleukin-17 from γδ T cells Th17 cells could stimulate proliferation of oral epithelial stem cells and their transformation which could be the initiating factor in OSCC pathogenesis. These could also contribute to progression of already established tumors and to therapy resistance. Interleukin-17 directly stimulates proliferation of tumor, prevents apoptosis leading to chemotherapy insensitivity. Moreover, IL-17 stimulates the production of G-CSF and GM-CSF, cytokines that expand, and chemokines that recruit myeloid cells, and neutrophils or granulocytic myeloid derived suppressor cells (MDSCs). These myeloid cells produce various angiogenic factors, MMPs, and promote tumor progression by stimulation of proliferation, survival, invasiveness, and metastasis and by suppressing antitumor immune activity of Tc17 and NK cells. Interleukin-17 stimulates cancer associated fibroblasts (CAFs) that produce mediators which promotes epithelial to mesenchymal transition and deposition of collagen resulting in escape from immune response. In addition, IL-17–induced protumoral cytokines, such as IL-6, function in a paracrine manner to enhance tumor growth and survival.
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