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IL21 Therapy Combined with PD-1 and Tim-3 Blockade Provides Enhanced NK Cell Antitumor Activity against MHC Class I-Deficient Tumors.

Authors
 Hyungseok Seo  ;  Byung-Seok Kim  ;  Eun-Ah Bae  ;  Byung Soh Min  ;  Yoon Dae Han  ;  Sang Joon Shin  ;  Chang-Yuil Kang 
Citation
 Cancer Immunology Research, Vol.6(6) : 685-695, 2018 
Journal Title
 Cancer Immunology Research 
ISSN
 2326-6066 
Issue Date
2018
Abstract
Increased expression of coinhibitory molecules such as PD-1 and Tim-3 on NK cells has been demonstrated in advanced cancer patients who harbor MHC class I-deficient tumors. However, even in preclinical models, the antitumor effects of checkpoint blockade on NK cells have not been clearly elucidated. Here, we show that anti-PD-1/anti-Tim-3 treatment suppressed tumor progression in mice bearing MHC class I-deficient tumors, and the suppression was further enhanced by recombinant IL21 (rIL21) treatments through an NK-cell-dependent mechanism. We also show that the intratumoral delivery of rIL21 attracted NK cells to the tumor site in a CXCR3-dependent fashion. A combination of IL21 and checkpoint blockade facilitated the effector function of exhausted NK cells in cancer patients. Given the effects of the checkpoint blockade and rIL21 combination on NK cells infiltrating into MHC class I-deficient tumors, we suggest that the efficacy of checkpoint blockade can be enhanced through the administration of IL21 for advanced cancer patients with MHC class I-low/deficient tumors. Cancer Immunol Res; 6(6); 685-95. ©2018 AACR.
Full Text
http://cancerimmunolres.aacrjournals.org/content/6/6/685.long
DOI
10.1158/2326-6066.CIR-17-0708
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
민병소(Min, Byung Soh)
신상준(Shin, Sang Joon)
한윤대(Han, Yoon Dae) ORCID logo https://orcid.org/0000-0002-2136-3578
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/165418
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