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

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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.

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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

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Acknowledgements

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

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    Authors and Affiliations

    1. College of Pharmacy, Chungbuk National University, 194-31 Osongsaengmyung-1, Heungdeok, Cheongju, Chungbuk, 28160, Republic of Korea

      Ji Sung Kim, Yong Guk Kim, Hong Kyung Lee, Eun Jae Park, Boyeong Kim, Heesoon Lee, Youngsoo Kim, Jin Tae Hong & Sang-Bae Han

    2. Korea Research Institute of Bioscience and Biotechnology, Cheongju, Chungbuk, 28116, Republic of Korea

      Jong Soon Kang

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    Ji Sung Kim and Yong Guk Kim are co-first authors and have contributed equally.

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    Kim, J.S., Kim, Y.G., Lee, H.K. et al. Cytokine-induced killer cells hunt individual cancer cells in droves in a mouse model. Cancer Immunol Immunother 66, 193–202 (2017). https://doi.org/10.1007/s00262-016-1934-2

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