Tumour-infiltrating bystander CD8(+) T cells activated by IL-15 contribute to tumour control in non-small cell lung cancer
- Authors
- Leem, Galam; Jeon, Minwoo; Kim, Kun Woo; Jeong, Seongju; Choi, Seong Jin; Lee, Yong Joon; Kim, Eui-Soon; Lee, Jae-Ik; Ha, Seung Yeon; Park, Su-Hyung; Shim, Hyo Sup; Lee, Jin Gu; Kang, Shin Myung; Shin, Eui-Cheol
- Issue Date
- Aug-2022
- Publisher
- BMJ PUBLISHING GROUP
- Keywords
- non-small cell lung cancer; lung cancer
- Citation
- THORAX, v.77, no.8, pp.769 - 780
- Journal Title
- THORAX
- Volume
- 77
- Number
- 8
- Start Page
- 769
- End Page
- 780
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/85234
- DOI
- 10.1136/thoraxjnl-2021-217001
- ISSN
- 0040-6376
- 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)-gamma (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)-gamma after IL-15 treatment, and that IL-15 treatment in MCMV-infected mice upregulated tumour necrosis factor-alpha and IFN-gamma 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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