Immunomodulatory aspects in the progression and treatment of oral malignancy

Nobuo Kondoh; Masako Mizuno-Kamiya; Naoki Umemura; Eiji Takayama; Harumi Kawaki; Kenji Mitsudo; Yasunori Muramatsu; Shinichiro Sumitomo

doi:10.1016/j.jdsr.2019.09.001

Immunomodulatory aspects in the progression and treatment of oral malignancy

Jpn Dent Sci Rev. 2019 Nov;55(1):113-120. doi: 10.1016/j.jdsr.2019.09.001. Epub 2019 Oct 7.

Authors

Nobuo Kondoh¹, Masako Mizuno-Kamiya², Naoki Umemura¹, Eiji Takayama¹, Harumi Kawaki¹, Kenji Mitsudo³, Yasunori Muramatsu⁴, Shinichiro Sumitomo⁴

Affiliations

¹ Department of Oral Biochemistry, Division of Oral Structure, Function and Development, Asahi University School of Dentistry, 1851-1 Hozumi, Mizuho, Gifu, 501-0296, Japan.
² Chemistry Laboratory, Department of Business Administration, Asahi University School of Business Administration, 1851-1 Hozumi, Mizuho, Gifu 501-0296, Japan.
³ Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
⁴ Department of Oral and Maxillofacial Surgery, Division of Oral Pathogenesis and Disease Control, Asahi University School of Dentistry, 1851-1 Hozumi, Mizuho, Gifu, 501-0296, Japan.

Abstract

Inflammation substantially affects the risk of oral malignancy. Pro-inflammatory cytokine, interferon (IFN)-γ, confers anti-tumor activity using several different mechanisms. Conversely, higher expression of interleukin (IL)-17 is associated with worse prognosis. Monocyte chemotactic protein (MCP)-1 correlates positively with poor long-term survival of head and neck squamous cell carcinoma (HNSCC) patients. IL-1α affects cancer associated fibroblasts and macrophages, and promote several malignant phenotypes including immune suppression. Some anti-inflammatory cytokines, including IL-10 and transforming growth factor (TGF)-β, relate to pro-tumoral activities. Among immune checkpoint modulators, programmed death (PD-)1 and PD-ligand (L)1 facilitate oral squamous cell carcinoma (OSCC) cell evasion from immune surveillance, and the expression status of these has a prognostic value. OSCCs contain tumor associated macrophages (TAMs) as major stromal cells of their tumor microenvironment. Among the two distinctive states, M2 macrophages support tumor invasion, metastasis and immune suppression. Crosstalk between TAMs and OSCC or cancer-associated fibroblasts (CAF) plays an important role in the progression of OSCC. Clinical trials with blocking antibodies against IL-1α or melanoma-associated antigens have been reported as therapeutic approaches against OSCCs. The most promising approach activating antitumor immunity is the blockade of PD-1/PD-L1 axis. Manipulating the polarization of pro-tumorigenic macrophages has been reported as a novel therapeutic approach.

Keywords: Cancer-associated fibroblast (CAF); IFN-γ; IL-1α; Immune suppression; Programmed death (PD)1; Programmed death ligand (PD-L)1; Tumor associated macrophage (TAM); Tumor microenvironment (TME).

Publication types

Review