title: Oral squamous cell carcinoma suppressed antitumor immunity through induction of PD-L1 expression on tumor-associated macrophages.
abstract: Oral squamous cell carcinoma (OSCC) is the most common solid tumor in the oral cavity. Development and progression of OSCC is associated with the elevated presence of inhibitory M2 type tumor-associated macrophages (TAMs). However, the underlying mechanism leading to the enrichment of M2 TAMs and the pathway through which TAMs foster tumor progression are still unclear. In this study, we harvested TAMs and tumor cells from primary OSCC resections of stage II and stage III patients. We showed that compared to peritumoral macrophages, TAMs presented upregulated expression of PD-L1 and elevated capacity in inducing T cell apoptosis. The level of PD-L1 expression directly correlated with the level of T cell apoptosis. Interestingly, peripheral blood monocytes with low initial PD-L1 level had upregulated PD-L1 expression and acquired the ability to induce T cell apoptosis, after incubation with primary tumor cells from OSCC patients. The PD-L1 expression by monocytes depended on interleukin 10 (IL-10), since blockade of IL-10 in the tumor-monocyte coculture abrogated PD-L1 upregulation. IL-10 mRNA expression in tumor cells and monocytes also preceded PD-L1 mRNA expression in monocytes. Furthermore, the IL-10 concentration in the tumor microenvironment directly correlated with the PD-L1 level on TAMs. Together, these results suggest that OSCC could directly suppress antitumor T cell immunity through conditioning TAMs.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, 410078, China.
authors.forename: Canhua
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, 410078, China.
authors.forename: Fulai
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Immunology, Xiangya School of Medicine, Central South University, Changsha, 410078, China. Electronic address: jiewang_cs@sina.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, 410078, China.
authors.forename: Limeng
authors.initials: L
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D060890:B7-H1 Antigen / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D056747:Immunomodulation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D009367:Neoplasm Staging; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology
chemical_list: D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human; D016207:Cytokines
keywords: Macrophages; Oral squamous cell carcinoma; PD-L1