Tumor regression is mediated via the induction of HER263-71- specific CD8+ CTL activity in a 4T1.2/HER2 tumor model: no involvement of CD80 in tumor control
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Sayyed Nilofar Danishmalik1, Si-Hyeong Lee1, Jeong-Im Sin1
1BK21 Plus Graduate Program and Department of Microbiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-701, Korea
Jeong-Im Sin, email: [email protected]
Keywords: antitumor immunity, CD80, MDSCs, HER2, tumor models
Received: April 24, 2016 Accepted: February 20, 2017 Published: March 01, 2017
In the CT26/HER2 and 4T1.2/HER2 tumor models, CT26/HER2 cells form tumors that continue to grow, whereas 4T1.2/HER2 cells form tumors that eventually regress. Here, we investigated the differences in the behaviors of these two cell lines. When immune cells from 4T1.2/HER2 tumor-bearing animals were stimulated with HER2 class I peptides, they displayed a 2-fold increase in IFN-γ levels, in response to the peptides, HER263–71 and HER2342–350. In contrast, extremely high levels of antigen-non-specific IFN-γ production were observed with immune cells and sera from CT26/HER2 tumor-bearing mice. However, IFN-γ had no effect on tumor progression in the CT26/HER2 model, as determined by an IFN-γ knockout assay. 4T1.2/HER2 tumor-bearing mice displayed CTL activity in response to HER263–71 but not to HER2342–350, whereas no such induction was observed in CT26/HER2 tumor-bearing mice. When 4T1.2/HER2 cell-challenged mice were depleted of CD8+ T cells, they lost their tumor-regressing activity, suggesting an antitumor role of HER263–71-specific CD8+ CTLs in the control of this tumor type. CT26/HER2 cells also expressed CD80. However, CD80-transfected 4T1.2/HER2 and CD80-non-expressing CT26/HER2 cells failed to alter their tumorigenicity, suggesting no role of CD80 in tumor control. Despite increased levels of myeloid-derived suppressor cells in the tumor, they were not associated with tumor progression in the CT26/HER2 model, as determined by a cell depletion assay. Overall, these data show that, contrary to CT26/HER2 tumors, 4T1.2/HER2 tumors regress via the induction of HER263–71-specific CD8+ CTLs and that CD80 is not associated with the regression of these tumors.
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