Heterotypic cell-in-cell structures between cancer and NK cells are associated with enhanced anticancer drug resistance
Yun-Jeong Choe,
Jin Young Min,
Hyunseong Lee,
Sang-Yeop Lee,
Joseph Kwon,
Hye-Jin Kim,
Jangho Lee,
Hyun Min Kim,
Hye Sun Park,
Mi Young Cho,
Ju-Yong Hyun,
Hye Min Kim,
Yong-Ho Chung,
Sang Keun Ha,
Hye Gwang Jeong,
Inpyo Choi,
Tae-Don Kim,
Kwan Soo Hong,
Eun Hee Han
Affiliations
Yun-Jeong Choe
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, South Korea
Jin Young Min
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, South Korea; Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 34134, South Korea
Hyunseong Lee
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, South Korea
Sang-Yeop Lee
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, South Korea
Joseph Kwon
Research Center for Materials Analysis, Korea Basic Science Institute, Daejeon 34133, South Korea
Hye-Jin Kim
Tomocube, Inc., Daejeon 34051, South Korea
Jangho Lee
Research Division of Food Functionality, Korea Food Research Institute, Jeollabuk-do 55365, South Korea
Hyun Min Kim
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, South Korea
Hye Sun Park
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, South Korea
Mi Young Cho
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, South Korea
Ju-Yong Hyun
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, South Korea
Hye Min Kim
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, South Korea; Korea University of Science and Technology (UST), Daejeon 34113, Republic of Korea
Yong-Ho Chung
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, South Korea; Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 34134, South Korea
Sang Keun Ha
Research Division of Food Functionality, Korea Food Research Institute, Jeollabuk-do 55365, South Korea; Korea University of Science and Technology (UST), Daejeon 34113, Republic of Korea
Hye Gwang Jeong
Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 34134, South Korea
Inpyo Choi
Korea University of Science and Technology (UST), Daejeon 34113, Republic of Korea; Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 34141, Republic of Korea
Tae-Don Kim
Korea University of Science and Technology (UST), Daejeon 34113, Republic of Korea; Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 34141, Republic of Korea
Kwan Soo Hong
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, South Korea; Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 34134, South Korea
Eun Hee Han
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, South Korea; Korea University of Science and Technology (UST), Daejeon 34113, Republic of Korea; Corresponding author
Summary: The heterotypic CIC structures formed of cancer and immune cells have been observed in tumor tissues. We aimed to assess the feasibility of using heterotypic CICs as a functional biomarker to predict NK susceptibility and drug resistance. The heterotypic CIC-forming cancer cells showed a lower response to NK cytotoxicity and higher proliferative ability than non-CIC cancer cells. After treatment with anticancer drugs, cancer cells that formed heterotypic CICs showed a higher resistance to anticancer drugs than non-CIC cancer cells. We also observed the formation of more CIC structures in cancer cells treated with anticancer drugs than in the non-treated group. Our results confirm the association between heterotypic CIC structures and anticancer drug resistance in CICs formed from NK and cancer cells. These results suggest a mechanism underlying immune evasion in heterotypic CIC cancer cells and provide insights into the anticancer drug resistance of cancer cells.
