title: A novel subset of B7-H3+CD14+HLA-DR-/lowmyeloid-derived suppressor cells are associated with progression of human NSCLC.
abstract: Myeloid-derived suppressor cells (MDSC) potently inhibit antitumor immune responses, and thereby promoti tumor progression and metastasis. However, the nature of human tumor-infiltrating MDSC remains poorly characterized. Here, we find B7-H3 is exclusively expressed on a subset of intratumoral CD14+HLA-DR-/lowMDSC but absent from adjacent normal lung tissues of patients with non-small cell lung carcinoma (NSCLC). Cytokine analysis revealed that B7-H3+CD14+HLA-DR-/lowMDSC (B7-H3+MDSC) produced higher levels of IL-10 and TNFα but lower levels of IL-1β and IL-6 when compared with B7-H3-CD14+HLA-DR-/lowmyeloid-derived suppressor cells (B7-H3-MDSC). In a murine lung cancer model, B7-H3+MDSCs were found only in the tumor microenvironment and their frequencies increased during tumor progression. Clinical data analysis indicated that a higher frequency of B7-H3+MDSCs was associated with reduced recurrence-free survival in patients with NSCLC. Taken together, we identify a novel subset of MDSCs within the tumor microenvironment that fosters tumor progression.
authors.affiliation: Clinical Immunology Laboratory; Soochow University ; Suzhou, China ; Institute of Medical Biotechnology; Soochow University ; Suzhou, China.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Institute of Medical Biotechnology; Soochow University ; Suzhou, China ; Department of Thoracic Surgery; The First Affiliated Hospital of Soochow University ; Suzhou, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Huang
authors.affiliation: Institute of Medical Biotechnology; Soochow University ; Suzhou, China.
authors.forename: Yibei
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Institute of Medical Biotechnology; Soochow University ; Suzhou, China.
authors.forename: Gehua
authors.initials: G
authors.lastname: Yu
authors.affiliation: Institute of Medical Biotechnology; Soochow University ; Suzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.affiliation: Institute of Medical Biotechnology; Soochow University ; Suzhou, China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Clinical Immunology Laboratory; Soochow University ; Suzhou, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Liu
authors.affiliation: Clinical Immunology Laboratory; Soochow University ; Suzhou, China.
authors.forename: Jianquan
authors.initials: J
authors.lastname: Hou
authors.affiliation: Clinical Immunology Laboratory; Soochow University ; Suzhou, China ; Institute of Medical Biotechnology; Soochow University ; Suzhou, China.
authors.forename: Xueguang
authors.initials: X
authors.lastname: Zhang
keywords: APC, antigen presenting cell; B7-H3; B7-H3+MDSC, B7-H3+CD14+HLA-DR−/low MDSC; B7-H3−MDSC, B7-H3−CD14+HLA-DR−/low MDSC; BM, bone marrow; DC, dendritic cell; EAE, experimental autoimmune encephalomyelitis; FACS, Fluorescence activated cell sorter; LLC, Lewis Lung Carcinoma; MDSC; MDSC, Myeloid-derived suppressor cell; NSCLC, Non-small cell lung carcinoma; RT-qPCR, real-time quantitative PCR; Treg; Tumor microenvironment; mTGFβ, membrane-bound TGFβ; non-small cell lung cancer