한빛사 논문
Galam Leem1, Minwoo Jeon2, Kun Woo Kim3, Seongju Jeong2, Seong Jin Choi2, Yong Joon Lee2, Eui-Soon Kim2, Jae-Ik Lee3, Seung Yeon Ha4, Su-Hyung Park2, Hyo Sup Shim5, Jin Gu Lee6, Shin Myung Kang7, Eui-Cheol Shin2
1Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
2Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea (the Republic of)
3Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Incheon, Korea (the Republic of)
4Department of Pathology, Gachon University Gil Medical Center, Incheon, Korea (the Republic of)
5Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
6Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea (the Republic of)
7Division of Pulmonology and Allergy, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea (the Republic of)
GL, MJ and KWK contributed equally.
Correspondence to Professor Eui-Cheol Shin, Dr Jin Gu Lee, Dr Shin Myung Kang
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.
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