title: CD163(+) M2-type tumor-associated macrophage support the suppression of tumor-infiltrating T cells in osteosarcoma.
abstract: Osteosarcoma is one of the most common childhood cancers with high numbers of cancer-related deaths. Progress in conventional therapies is showing limited improvement. An adaptive T cell-based immunotherapy represents a promising new therapeutic option, but to improve its efficacy, regulatory mechanisms in osteosarcoma need further elucidation. Here, to evaluate the regulatory effect of tumor microenvironment of T cells in osteosarcoma, we examined the peripheral blood (PB) and tumor infiltrating (TI) T cells, and their correlations with PB and tumor immune characteristics. We found that TI T cells contained significantly higher levels of TIM-3(+)PD-1(-) and TIM-3(+)PD-1(+) cells than their PB counterparts. Similar to that in chronic HIV and HCV infections, these TIM-3(+)PD-1(-) and TIM-3(+)PD-1(+) T cells presented reduced proliferation and proinflammatory cytokine secretion in response to stimulation. Presence of M2-type (CD163(+)) macrophages exacerbated T cell immunosuppression, since frequencies of CD163(+) tumor-associated macrophages were directly correlated with the frequencies of suppressed TIM-3(+)PD-1(+) T cells. Moreover, depletion of CD163(+) macrophages significantly improved T cell proliferation and proinflammatory cytokine production. Overall, our data presented an intratumoral T cell-specific immunosuppression that was amplified by M2-type tumor-associated macrophages.
authors.affiliation: Surgical Research Laboratory, The Affiliated Hospital of Nantong University, Nantong, Jiangsu, China. Electronic address: qinglinhan_nt@sina.com.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Han
authors.affiliation: Surgical Research Laboratory, The Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors.forename: Hongguang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Surgical Research Laboratory, The Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000637:transplantation; D008264:Macrophages / Q000276:immunology*; D012516:Osteosarcoma / Q000276:immunology* / Q000628:therapy; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D019139:Tumor Escape; D059016:Tumor Microenvironment; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D016207:Cytokines; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011956:Receptors, Cell Surface
keywords: Macrophage; Osteosarcoma; PD-1; TIM-3