Type I interferon (IFN-I) plays a critical role in antiviral and antitumor defense. In our previous studies, we showed that IFN-I-inducible 2′–5′ oligoadenylate synthetase-like 1 (OASL1) negatively regulates IFN-I production upon viral infection by specifically inhibiting translation of the IFN-I-regulating master transcription factor, interferon regulatory factor 7 (IRF7). In this study, we investigated whether OASL1 plays a negative role in the anti-tumor immune response by using OASL1-deficient (Oasl1−/−) mice and transplantable syngeneic tumor cell models. We found that Oasl1−/− mice demonstrate enhanced resistance to lung metastatic tumors and subcutaneously implanted tumors compared to wild-type (WT) mice. Additionally, we found that cytotoxic effector cells such as CD8+ T cells (including tumor antigen-specific CD8+ T cells) and NK cells as well as CD8α+ DCs (the major antigen cross-presenting cells) were much more frequent (>fivefold) in the Oasl1−/− mouse tumors. Furthermore, the cytotoxic effector cells in Oasl1−/− mouse tumors seemed to be more functionally active. However, the proportion of immunosuppressive myeloid-derived suppressor cells within hematopoietic cells and of regulatory T cells within CD4+ T cells in Oasl1−/− mouse tumors did not differ significantly from that of WT mice. Tumor-challenged Oasl1−/− mice expressed increased levels of IFN-I and IRF7 protein in the growing tumor, indicating that the enhanced antitumor immune response observed in Oasl1−/− mice was caused by higher IFN-I production in Oasl1−/− mice. Collectively, these results show that OASL1 deficiency promotes the antitumor immune response, and thus, OASL1 could be a good therapeutic target for treating tumors.
Bibliographical noteFunding Information:
We thank the members of the Molecular Immunology and Medicine (MoIM) Lab and SJ Ryu for their support. This study was supported by the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology (NRF-2013R1A1A2058447); Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare (HI14C2449).
© 2016, Springer-Verlag Berlin Heidelberg.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Cancer Research