IL-10 Contributes to the Suppressive Function of Tumour-Associated Myeloid Cells and Enhances Myeloid Cell Accumulation in Tumours

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...

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Veröffentlicht in:Scandinavian journal of immunology 2012-03, Vol.75 (3), p.273-281
Hauptverfasser: Wang, L.-X., Talebian, F., Liu, J.-Q., Khattabi, M., Yu, L., Bai, X.-F.
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Sprache:eng
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Zusammenfassung: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.
ISSN:0300-9475
1365-3083
DOI:10.1111/j.1365-3083.2011.02662.x