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Cancer Immunology, Immunotherapy

, Volume 66, Issue 2, pp 193–202 | Cite as

Cytokine-induced killer cells hunt individual cancer cells in droves in a mouse model

  • Ji Sung Kim
  • Yong Guk Kim
  • Hong Kyung Lee
  • Eun Jae Park
  • Boyeong Kim
  • Jong Soon Kang
  • Heesoon Lee
  • Youngsoo Kim
  • Jin Tae Hong
  • Sang-Bae HanEmail author
Original Article

Abstract

Cytotoxicity of cytokine-induced killer (CIK) cells depends mainly on their encounters with target cells, but how many CIK cells are required to kill an individual cancer cell is unknown. Here we used time-lapse imaging to quantify the critical effector cell number required to kill an individual target cell. CIK cells killed MHC-I-negative and MHC-I-positive cancer cells, but natural killer (NK) cells destroyed MHC-I-negative cells only. The average threshold number of CIK cells required to kill an individual cancer cell was 6.7 for MHC-I-negative cells and 6.9 for MHC-I-positive cells. That of NK cells was 2.4 for MHC-I-negative cells. Likely due to the higher threshold numbers, killing by CIK cells was delayed in comparison with NK cells: 40% of MHC-negative target cells were killed after 5 h when co-cultured with CIK cells and after 2 h with NK cells. Our data have implications for the rational design of CIK cell-based immunotherapy of cancer patients.

Keywords

Cytotoxicity Natural killer cells Threshold number Time-lapse imaging 

Abbreviations

APC

Allophycocyanin

Calcein-AM

Calcein acetoxymethyl ester

CIK

Cytokine-induced killer

DNAM-1

DNAX accessory molecule-1

FasL

Fas ligand

MS

Mesenchymal stem cell

NKG2A

NK group 2 member A

NKG2D

NK group 2 member D

SEM

Standard error of the mean

TIGIT

T-cell immunoglobulin and ITIM domain

Notes

Acknowledgements

This study was supported by a grant funded by the Korean Government (NRF-2008-0062275).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

262_2016_1934_MOESM1_ESM.pdf (17 kb)
Supplementary material 1 (PDF 16 kb)

Supplementary material 2 (MP4 1113 kb)

Supplementary material 3 (MP4 1016 kb)

Supplementary material 4 (MP4 1287 kb)

Supplementary material 5 (MP4 1551 kb)

Supplementary material 6 (MP4 375 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Ji Sung Kim
    • 1
  • Yong Guk Kim
    • 1
  • Hong Kyung Lee
    • 1
  • Eun Jae Park
    • 1
  • Boyeong Kim
    • 1
  • Jong Soon Kang
    • 2
  • Heesoon Lee
    • 1
  • Youngsoo Kim
    • 1
  • Jin Tae Hong
    • 1
  • Sang-Bae Han
    • 1
    Email author
  1. 1.College of PharmacyChungbuk National UniversityCheongjuRepublic of Korea
  2. 2.Korea Research Institute of Bioscience and BiotechnologyCheongjuRepublic of Korea

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