2′–5′ Oligoadenylate synthetase-like 1 (OASL1) deficiency in mice promotes an effective anti-tumor immune response by enhancing the production of type I interferons

Chan Kyu Sim, Yeon Sook Cho, Byung Soo Kim, In Jeoung Baek, Young Joon Kim, Myeong Sup Lee

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)663-675
Number of pages13
JournalCancer Immunology, Immunotherapy
Volume65
Issue number6
DOIs
Publication statusPublished - 2016 Jun 1

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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