1528P - Repeated exposure to cisplatin enhances NK cell-mediated cytotoxicity via up-regulation of NKG2D ligands in non-small cell lung cancer cells

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Riki Okita
Citation Annals of Oncology (2016) 27 (6): 526-544. 10.1093/annonc/mdw392
Authors R. Okita, Y. Nojima, A. Maeda, S. Saisho, K. Shimizu, M. Nakata
  • General Thoracic Surgery, Kawasaki Medical School Hospital, 7010192 - Okayama/JP



Cisplatin (CDDP) is one of the key drugs for non-small cell lung cancer (NSCLC) and CDDP-resistant mechanisms have been investigated, while the role of immune cells on excluding CDDP-treated cancer cells is poorly understood. Here we demonstrate repeated exposure to CDDP enhances NK group 2 member D (NKG2D) ligands MHC class I-related chain A and B (MICA/B) and UL16 binding protein (ULBP)-2/5/6 in NSCLC cell lines while attenuates them in tumor tissue from patients with NSCLC.


A549 cells were exposed to 10 µM of CDDP (A549-CR) at least thrice then possible influences of CDDP exposure on expressions of MICA/B and ULBP-2/5/6 were investigated by flow cytometry. NK cell-mediated cytotoxicity against A549-CR cells was assessed by LDH release assay and compared with original A549 cells. The expressions of NKG2D ligands in tissue samples from NSCLC patients who received CDDP-base chemotherapy were also evaluated using immunohistochemical reactions.


Basal expression of MICA/B and ULBP-2/5/6 were clearly upregulated in A549-CR cells compared with original A549 cells. As expected, NK cell-mediated cytotoxicity was enhanced against A549-CR cells compared with A549 cells, and this enhancement depended on NKG2D-NKG2D ligands interaction. On the other hand, the expression of MICA/B and ULBP-2/5/6 were lower in residual tumor than in pre-treated samples from patients with NSCLC.


Repeated CDDP exposure enhances the expression of NKG2D ligands in A549 cell line, resulted in enhanced NK cell-mediated cytotoxicity in vitro. On the other hand, repeated CDDP exposure attenuated the expression of NKG2D ligands in patients with NSCLC, suggested that the residual tumor was the result of tumor immunoescape from NK cells.

Clinical trial identification

Legal entity responsible for the study

Kawasaki Medical School


This work was supported by the Japan Society for the Promotion of Science (JSPS) Kakenhi Grant (25462189) to R Okita. Dr. M Nakata received research funding from Kyowa Kirin for this study.


M. Nakata: Research funding from Kyowa Kirin. All other authors have declared no conflicts of interest.