RT Journal Article SR Electronic T1 Tumour-infiltrating bystander CD8+ T cells activated by IL-15 contribute to tumour control in non-small cell lung cancer JF Thorax JO Thorax FD BMJ Publishing Group Ltd and British Thoracic Society SP 769 OP 780 DO 10.1136/thoraxjnl-2021-217001 VO 77 IS 8 A1 Galam Leem A1 Minwoo Jeon A1 Kun Woo Kim A1 Seongju Jeong A1 Seong Jin Choi A1 Yong Joon Lee A1 Eui-Soon Kim A1 Jae-Ik Lee A1 Seung Yeon Ha A1 Su-Hyung Park A1 Hyo Sup Shim A1 Jin Gu Lee A1 Shin Myung Kang A1 Eui-Cheol Shin YR 2022 UL http://thorax.bmj.com/content/77/8/769.abstract AB 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.RNA sequencing data are uploaded on Gene Expression Omnibus (GEO) database. GEO accession number is GSE185243. All other data that support the findings of this study are available from the corresponding author ECS upon reasonable request.