title: IL-10 contributes to the suppressive function of tumour-associated myeloid cells and enhances myeloid cell accumulation in tumours.
abstract: Studies have revealed that tumour-associated myeloid cells (TAMC) are one of the major sources of IL-10 in tumour-bearing mice. However, the significance of TAMC-derived IL-10 in tumour immunity is poorly understood. Here, we show that IL-10 blockade or IL-10 deficiency reduces the capacity of TAMC in suppressing the proliferation of P1A-specific CD8 T cells. In the spleen, IL-10-deficient and wild-type (WT) mice bearing large tumour burdens have similar TAMC populations. The tumours from IL-10-deficient mice, however, have reduced numbers of TAMC compared with tumours from their WT counterparts. IL-10⁻/⁻ RAG-2⁻/⁻ mice also had reduced numbers of TAMC compared with tumours from IL-10⁺/⁺ RAG-2⁻/⁻ mice; therefore, the reduction in TAMC in IL-10-deficient tumours was not because of adaptive immune response in tumours. Adoptively transferred tumour antigen-specific CD8 T cells expanded more efficiently within tumours in IL-10⁻/⁻ RAG-2⁻/⁻ mice than in tumours from IL-10⁺/⁺ RAG-2⁻/⁻ mice. Cytotoxic T lymphocyte adoptive transfer therapy prevented tumour evasion in IL-10⁻/⁻ RAG-2⁻/⁻ mice more efficiently than in IL-10⁺/⁺ RAG-2⁻/⁻ mice. Thus, IL-10 enhances the accumulation of myeloid cells in tumours, and TAMC-derived IL-10 suppresses the activation and expansion of tumour antigen-specific T cells.
authors: Department of Pathology and Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, OH, USA.
authors: L-X
authors: LX
authors: Wang
authors: F
authors: F
authors: Talebian
authors: J-Q
authors: JQ
authors: Liu
authors: M
authors: M
authors: Khattabi
authors: L
authors: L
authors: Yu
authors: X-F
authors: XF
authors: Bai
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000276:immunology; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology
chemical_list: D039481:CD11b Antigen; D004273:DNA, Neoplasm; D011956:Receptors, Cell Surface; C551746:granulocyte receptor 1, mouse; D016753:Interleukin-10