Heterotypic cell-in-cell structures between cancer and NK cells are associated with enhanced anticancer drug resistance
Yun-Jeong Choe, Jin Young Min, Hyunseung Lee, Sang-Yeop Lee, Joseph Sang‐Il 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
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.