title: Immunosuppression Induced by Chronic Inflammation and the Progression to Oral Squamous Cell Carcinoma.
abstract: Oral squamous cell carcinoma (OSCC) is an aggressive, invasive malignancy of epithelial origin. The progression from premalignant lesions-oral leukoplakia (OLK) and oral lichen planus (OLP)-to OSCC involves complex inflammatory processes that have not been elucidated. We investigated the roles of inflammatory mediators and infiltrating immunocytes in the pathogenic progression of OLK and OLP to OSCC. The occurrence of regulatory T-cells (Tregs) and tumor-associated macrophages (TAMs) and the expression of anti-inflammatory cytokines and proinflammatory cytokines were investigated in OLK, OLP, and OSCC tissues. Immunohistochemical staining of CD4, FOXP3, CD68, TGF-β1, IL-10, IL-4, IFN-γ, and MCP-1 showed that the occurrence of Tregs and TAMs increased in parallel with disease progression in OLK and OSCC. IL-10 gradually increased during the early stages of OLK and in OSCC. Infiltrating IL-4+macrophages were seen with increasing frequency in OLK tissue during the progression of oral dysplasia. Fewer TGF-β1+macrophages were seen in OSCC than in OLK and OLP. The expression of IFN-γdecreased gradually with the OLK development and had the lowest expression in OSCC. MCP-1 expression did not change significantly during the development of OSCC. The results suggested that the immunosuppression induced by chronic inflammation promotes tumorigenesis in OSCC, rather than initiating it.
authors.affiliation: Department of Periodontal & Oral Medicine, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Stomatology, Beijing Tongren Hospital, Capital Medical University, Beijing 100005, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Periodontal & Oral Medicine, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Guan
authors.affiliation: Department of Periodontal & Oral Medicine, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Hongru
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Periodontal & Oral Medicine, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: Zheng
authors.identifier: 0000-0001-7427-087X
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China.
authors.forename: Hui
authors.identifier: 0000-0002-7456-6061
authors.initials: H
authors.lastname: Zeng
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D018932:Chemokine CCL2 / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000473:pathology*; D015847:Interleukin-4 / Q000378:metabolism; D007972:Leukoplakia, Oral / Q000473:pathology; D017676:Lichen Planus, Oral / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; C508598:IL4 protein, human; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4