IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting

Takeda, Kazuyoshi, Nakayama, Masafumi , Hayakawa, Yoshihiro, Kojima, Yuko, Ikeda, Hiroaki, Imai, Naoko, Ogasawara, Kouetsu, Okumura, Ko, Thomas, David M. and Smyth, Mark J. (2017) IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting. Nature Communications, 8 . doi:10.1038/ncomms14607

Author Takeda, Kazuyoshi
Nakayama, Masafumi
Hayakawa, Yoshihiro
Kojima, Yuko
Ikeda, Hiroaki
Imai, Naoko
Ogasawara, Kouetsu
Okumura, Ko
Thomas, David M.
Smyth, Mark J.
Title IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2017-02-24
Sub-type Article (original research)
DOI 10.1038/ncomms14607
Open Access Status DOI
Volume 8
Total pages 13
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2018
Language eng
Formatted abstract
Genetic evolution that occurs during cancer progression enables tumour heterogeneity, thereby fostering tumour adaptation, therapeutic resistance and metastatic potential. Immune responses are known to select (immunoedit) tumour cells displaying immunoevasive properties. Here we address the role of IFN-γ in mediating the immunoediting process. We observe that, in several mouse tumour models such as HA-expressing 4T1 mammary carcinoma cells, OVA-expressing EG7 lymphoma cells and CMS5 MCA-induced fibrosarcoma cells naturally expressing mutated extracellular signal-regulated kinase (ERK) antigen, the action of antigen-specific cytotoxic T cell (CTL) in vivo results in the emergence of resistant cancer cell clones only in the presence of IFN-γ within the tumour microenvironment. Moreover, we show that exposure of tumours to IFN-γ-producing antigen-specific CTLs in vivo results in copy-number alterations (CNAs) associated with DNA damage response and modulation of DNA editing/repair gene expression. These results suggest that enhanced genetic instability might be one of the mechanisms by which CTLs and IFN-γ immunoedits tumours, altering their immune resistance as a result of genetic evolution.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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School of Medicine Publications
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