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髓系来源的抑制性细胞对内源性和过继转移 T 细胞的影响。

Myeloid-derived suppressor cell impact on endogenous and adoptively transferred T cells.

机构信息

Department of Radiation and Cellular Oncology, The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA.

Verona University Hospital, Department of Pathology and Diagnostics, 37134 Verona, Italy.

出版信息

Curr Opin Immunol. 2015 Apr;33:120-5. doi: 10.1016/j.coi.2015.02.006. Epub 2015 Feb 27.

Abstract

Novel models of autochthonous tumorigenesis and adoptive T cell therapy (ATT) are providing new clues regarding the pro-tumorigenic and immunosuppressive effects of myeloid-derived suppressor cells (MDSC), and their interaction with T cells. New findings are shifting the perception of the main level at which MDSC act, from direct cell-to-cell suppression to others, such as limiting T cell infiltration. Adoptively transferred, high-avidity T cells recognizing peptides with high-affinity for MHC-I eliminated large tumors. However, low-avidity T cells or low-affinity peptides resulted in failure to eradicate tumors. Manipulation of intratumoral myeloid cells improved the outcome of otherwise unsuccessful ATT. Therefore, therapeutic intervention directed at the tumor stroma might be required when using suboptimal T cells for ATT.

摘要

新型的自发肿瘤发生模型和过继性 T 细胞治疗(ATT)为髓系来源的抑制细胞(MDSC)的促肿瘤和免疫抑制作用及其与 T 细胞的相互作用提供了新的线索。新发现改变了 MDSC 作用的主要水平的认识,从直接的细胞间抑制到其他水平,如限制 T 细胞浸润。识别与 MHC-I 具有高亲和力的肽的高亲和力、过继转移的 T 细胞消除了大肿瘤。然而,低亲和力 T 细胞或低亲和力肽导致肿瘤无法根除。对肿瘤内髓样细胞的操纵改善了 otherwise unsuccessful ATT 的结果。因此,当使用次优 T 细胞进行 ATT 时,可能需要针对肿瘤基质的治疗干预。

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