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.