Induction of immunogenic cell death by radiation-upregulated karyopherin alpha 2 in vitro.

Accumulating evidence suggests the potential for radiation therapy to generate antitumor immune responses against tumor cells by inducing immunogenic cell death and phenotypic changes. We recently found that ionizing radiation upregulated karyopherin α2 in HT-29 colorectal tumor cells using quantitative proteomic analysis. To determine whether this increased could function as a damage-associated molecular pattern to induce antitumor immune responses, mouse bone-marrow-derived dendritic cells (BMDCs) were treated with Kduanyu15352 enhanced the surface expression of CD40, CD54, CD80, CD86, and MHC class I/II on BMDCs. DCs treated with Kduanyu15352 exhibited increased secretion of pro-inflammatory cytokines such as IL-1β, IL-6, IL-12, IL-23, and TNF-α. Co-culture of CD4(+) T cells and DCs resulted in induction of Th1/17 cytokines (IFN-γ and IL-17) and reduction of TGF-β production. Moreover, Kduanyu15352-treated DCs were capable of increasing granzyme B and perforin expression in cytotoxic T lymphocytes. These results demonstrated that radiation-induced dying colorectal cancer cells released considerable amounts of Kduanyu15352 that induce the maturation and activation of DCs for synergistic antitumor effect of radiation.

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