1. Tumour-infiltrating bystander CD8+T cells activated by IL-15 contribute to tumour control in non-small cell lung cancer
- Author
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Su-Hyung Park, Eui-Soon Kim, Jin Gu Lee, Yong Joon Lee, Seongjin Choi, Kun Woo Kim, Hyo Sup Shim, Minwoo Jeon, Eui-Cheol Shin, Jae-Ik Lee, Seongju Jeong, Seung Yeon Ha, Galam Leem, and Shin Myung Kang
- Subjects
Pulmonary and Respiratory Medicine ,business.industry ,Interleukin ,NKG2D ,Antigen ,Interleukin 15 ,Interferon ,Cancer research ,Bystander effect ,Cytotoxic T cell ,Medicine ,business ,CD8 ,medicine.drug - Abstract
BackgroundTumour-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.MethodsWe 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.ResultsWe 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.ConclusionThus, the study demonstrates that bystander CD8+TILs can be repurposed by IL-15 for tumour immunotherapy.
- Published
- 2021