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

doi:10.1016/j.isci.2022.105017

Heterotypic cell-in-cell structures between cancer and NK cells are associated with enhanced anticancer drug resistance

iScience. 2022 Aug 27;25(9):105017. doi: 10.1016/j.isci.2022.105017. eCollection 2022 Sep 16.

Authors

Yun-Jeong Choe¹, Jin Young Min^{1

2}, Hyunseong Lee¹, Sang-Yeop Lee¹, Joseph Kwon³, Hye-Jin Kim⁴, Jangho Lee⁵, Hyun Min Kim¹, Hye Sun Park¹, Mi Young Cho¹, Ju-Yong Hyun¹, Hye Min Kim^{1

6}, Yong-Ho Chung^{1

7}, Sang Keun Ha^{5

6}, Hye Gwang Jeong², Inpyo Choi^{6

8}, Tae-Don Kim^{6

8}, Kwan Soo Hong^{1

7}, Eun Hee Han^{1

6}

Affiliations

¹ Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, South Korea.
² Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 34134, South Korea.
³ Research Center for Materials Analysis, Korea Basic Science Institute, Daejeon 34133, South Korea.
⁴ Tomocube, Inc., Daejeon 34051, South Korea.
⁵ Research Division of Food Functionality, Korea Food Research Institute, Jeollabuk-do 55365, South Korea.
⁶ Korea University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
⁷ Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 34134, South Korea.
⁸ Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 34141, Republic of Korea.

Abstract

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.

Keywords: Biophysics; Cancer; Cell biology.