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Tumour-infiltrating bystander CD8 + T cells activated by IL-15 contribute to tumour control in non-small cell lung cancer

Authors
 Galam Leem  ;  Minwoo Jeon  ;  Kun Woo Kim  ;  Seongju Jeong  ;  Seong Jin Choi  ;  Yong Joon Lee  ;  Eui-Soon Kim  ;  Jae-Ik Lee  ;  Seung Yeon Ha  ;  Su-Hyung Park  ;  Hyo Sup Shim  ;  Jin Gu Lee  ;  Shin Myung Kang  ;  Eui-Cheol Shin 
Citation
 LUNG CANCER, Vol.77(8) : 769-780, 2022-08 
Journal Title
LUNG CANCER
ISSN
 0169-5002 
Issue Date
2022-08
MeSH
Animals ; CD8-Positive T-Lymphocytes / metabolism ; CD8-Positive T-Lymphocytes / pathology ; Carcinoma, Non-Small-Cell Lung* / pathology ; Humans ; Interferon-gamma / metabolism ; Interleukin-15 / metabolism ; Interleukin-15 / pharmacology ; Lung Neoplasms* / pathology ; Mice ; NK Cell Lectin-Like Receptor Subfamily K / metabolism ; Tumor Microenvironment
Keywords
lung cancer ; non-small cell lung cancer
Abstract
Background: Tumour-unrelated, virus-specific bystander CD8+ T cells were recently shown to be abundant among tumour-infiltrating lymphocytes (TILs). However, their roles in tumour immunity have not been elucidated yet.

Methods: We studied the characteristics of bystander CD8+ TILs from non-small cell lung cancer (NSCLC) tissues (N=66) and their activation by interleukin (IL)-15 to repurpose them for tumour immunotherapy.

Results: We show that bystander CD8+ TILs specific to various viruses are present in human NSCLC tissues. We stimulated CD8+ TILs ex vivo using IL-15 without cognate antigens and found that IL-15 treatment upregulated NKG2D expression on CD8+ TILs, resulting in NKG2D-dependent production of interferon (IFN)-γ (p=0.0006). Finally, we tested whether IL-15 treatment can control tumour growth in a murine NSCLC model with or without a history of murine cytomegalovirus (MCMV) infection. IL-15 treatment reduced the number of tumour nodules in the lung only in mice with MCMV infection (p=0.0037). We confirmed that MCMV-specific bystander CD8+ TILs produced interferon (IFN)-γ after IL-15 treatment, and that IL-15 treatment in MCMV-infected mice upregulated tumour necrosis factor-α and IFN-γ responsive genes in tumour microenvironment.

Conclusion: Thus, the study demonstrates that bystander CD8+ TILs can be repurposed by IL-15 for tumour immunotherapy.
Full Text
https://thorax.bmj.com/content/77/8/769.long
DOI
10.1136/thoraxjnl-2021-217001
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
Yonsei Authors
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Lee, Jin Gu(이진구)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/190685
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