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- W2080723132 abstract "IL-12 and doxorubicin treatment are known to polarize anti-tumor immune response and induce tumor cell death, respectively, when each is administered alone. IL-12 treatment can boost NKG2D receptor expression on immune cells, enhancing NK cell cytotoxicity against different tumor cell lines. However, IL-12 treatment alone can only modestly increase expression of NKG2D receptor. In tumor immuno-surveillance, it is important to create an environment in which spleen cells constitutively express the NKG2D receptor thereby triggering NKG2D-dependent tumor cell death. In an earlier study, we found that coadministration of the anti-neoplastic drug doxorubicin and IL-12 greatly boosted anti-tumor efficacy. This increased anti-tumor efficacy was associated with a substantial increase in immune cell infiltration at tumor sites, but the underlying mechanism by which the increased number of immune cells was trafficked into the tumors remains largely unknown. This report demonstrates that doxorubicin plus IL-12 treatment induces the higher expression of NKG2D receptor in CD8 T cells than IL-12 treatment alone, resulting in an increased infiltration of NKG2D-positive CD8 T cells, and leading to an NKG2D-dependent tumor growth inhibition in vivo. These in vivo observations are in agreement with our in vitro result, in which the encounter between NKG2D receptor-positive effector cells and NKG2D ligand-positive tumor cells yields an NKG2D-dependent tumor cell death as determined by cytolytic activity assay. Blocking the NKG2D receptor by using neutralization antibody impaired doxorubicin plus IL-12 treatment-mediated tumor eradication in vivo and effector cell-mediated tumor cell death in vitro. Together, the evidence links the higher IL-12 plus doxorubicin treatment-induced NKG2D expression to greater CD8 T cell infiltration into tumors, tumor cell death, and anti-tumor efficacy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 404. doi:1538-7445.AM2012-404" @default.
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- W2080723132 date "2012-04-15" @default.
- W2080723132 modified "2023-09-27" @default.
- W2080723132 title "Abstract 404: Regulation of NKG2D expression and NKG2D-positive T cell tumor-specific trafficking by doxorubicin and IL-12in vivo" @default.
- W2080723132 doi "https://doi.org/10.1158/1538-7445.am2012-404" @default.
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