바로가기  >

Abstract

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 (KPNA2) in HT-29 colorectal tumor cells using quantitative proteomic analysis. To determine whether this increased KPNA2 could function as a damage-associated molecular pattern to induce antitumor immune responses, mouse bone-marrow-derived dendritic cells (BMDCs) were treated with KPNA2. KPNA2 enhanced the surface expression of CD40, CD54, CD80, CD86, and MHC class I/II on BMDCs. DCs treated with KPNA2 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 KPNA2-treated DCs resulted in induction of Th1/17 cytokines (IFN-γ and IL-17) and reduction of TGF-β production. Moreover, KPNA2-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 KPNA2 that induce the maturation and activation of DCs for synergistic antitumor effect of radiation.

Author information

Song KH1, Jung SY1, Kang SM1, Kim MH1, Ahn J1, Hwang SG1, Lee JH2, Lim DS3, Nam SY4, Song JY5.​

1Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea.

2Department of Biotechnology, CHA University, Gyeonggi-do 11160, Republic of Korea.

3Department of Biotechnology, CHA University, Gyeonggi-do 11160, Republic of Korea. Electronic address: dslim@cha.ac.kr.

4Low-Dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co., Ltd., Seoul 01450, Republic of Korea.

5Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea. Electronic address: immu@kirams.re.kr.