Enhanced Antitumor Immune Response in 2′-5′ Oligoadenylate Synthetase-Like 1- (OASL1-) Deficient Mice upon Cisplatin Chemotherapy and Radiotherapy
Type I interferon (IFN-I) plays a critical role in the antitumor immune response. In our previous study, we showed that IFN-I-inducible 2′-5′ oligoadenylate synthetase-like 1 (OASL1) negatively regulated IFN-I production upon tumor challenge similar to that of viral infection. Thus, OASL1-deficient...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2019/7596786 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832555442748784640 |
|---|---|
| author | Chan Kyu Sim Jung Hoon Lee In-Jeoung Baek Sang-Wook Lee Myeong Sup Lee |
| author_facet | Chan Kyu Sim Jung Hoon Lee In-Jeoung Baek Sang-Wook Lee Myeong Sup Lee |
| author_sort | Chan Kyu Sim |
| collection | DOAJ |
| description | Type I interferon (IFN-I) plays a critical role in the antitumor immune response. In our previous study, we showed that IFN-I-inducible 2′-5′ oligoadenylate synthetase-like 1 (OASL1) negatively regulated IFN-I production upon tumor challenge similar to that of viral infection. Thus, OASL1-deficient (Oasl1−/−) mice were more resistant to implanted tumor growth than wild-type (WT) mice. In this study, we investigated whether targeting or suppressing OASL1 could show synergistic effects on tumor clearance with conventional cancer therapies (such as chemotherapy and radiotherapy) using Oasl1−/− mice and a transplantable lung metastatic tumor cell model. Upon treatment with the anticancer drug cisplatin, we found that Oasl1−/− mice showed enhanced resistance to injected tumors compared to untreated Oasl1−/− mice. Similarly, irradiated Oasl1−/− mice showed better resistance to tumor challenge than untreated Oasl1−/− mice. Additionally, we found that Oasl1−/− mice applied with both types of the cancer therapies contained more cytotoxic effector cells, such as CD8+ T cells and NK cells, and produced more cytotoxic effector cytokine IFN-γ as well as IFN-I in their tumor-containing lungs compared to untreated Oasl1−/− mice. Collectively, these results show that targeting OASL1 together with conventional cancer therapies could be an effective strategy to enhance treatment efficacy. |
| format | Article |
| id | doaj-art-c2e175f85b924fe28e069f8273424992 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-c2e175f85b924fe28e069f82734249922025-02-03T05:48:14ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/75967867596786Enhanced Antitumor Immune Response in 2′-5′ Oligoadenylate Synthetase-Like 1- (OASL1-) Deficient Mice upon Cisplatin Chemotherapy and RadiotherapyChan Kyu Sim0Jung Hoon Lee1In-Jeoung Baek2Sang-Wook Lee3Myeong Sup Lee4Laboratory of Molecular Immunology and Medicine, Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of KoreaLaboratory of Molecular Immunology and Medicine, Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of KoreaDepartment of Convergence Medicine, Asan Institutes for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of KoreaDepartment of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of KoreaLaboratory of Molecular Immunology and Medicine, Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of KoreaType I interferon (IFN-I) plays a critical role in the antitumor immune response. In our previous study, we showed that IFN-I-inducible 2′-5′ oligoadenylate synthetase-like 1 (OASL1) negatively regulated IFN-I production upon tumor challenge similar to that of viral infection. Thus, OASL1-deficient (Oasl1−/−) mice were more resistant to implanted tumor growth than wild-type (WT) mice. In this study, we investigated whether targeting or suppressing OASL1 could show synergistic effects on tumor clearance with conventional cancer therapies (such as chemotherapy and radiotherapy) using Oasl1−/− mice and a transplantable lung metastatic tumor cell model. Upon treatment with the anticancer drug cisplatin, we found that Oasl1−/− mice showed enhanced resistance to injected tumors compared to untreated Oasl1−/− mice. Similarly, irradiated Oasl1−/− mice showed better resistance to tumor challenge than untreated Oasl1−/− mice. Additionally, we found that Oasl1−/− mice applied with both types of the cancer therapies contained more cytotoxic effector cells, such as CD8+ T cells and NK cells, and produced more cytotoxic effector cytokine IFN-γ as well as IFN-I in their tumor-containing lungs compared to untreated Oasl1−/− mice. Collectively, these results show that targeting OASL1 together with conventional cancer therapies could be an effective strategy to enhance treatment efficacy.http://dx.doi.org/10.1155/2019/7596786 |
| spellingShingle | Chan Kyu Sim Jung Hoon Lee In-Jeoung Baek Sang-Wook Lee Myeong Sup Lee Enhanced Antitumor Immune Response in 2′-5′ Oligoadenylate Synthetase-Like 1- (OASL1-) Deficient Mice upon Cisplatin Chemotherapy and Radiotherapy Journal of Immunology Research |
| title | Enhanced Antitumor Immune Response in 2′-5′ Oligoadenylate Synthetase-Like 1- (OASL1-) Deficient Mice upon Cisplatin Chemotherapy and Radiotherapy |
| title_full | Enhanced Antitumor Immune Response in 2′-5′ Oligoadenylate Synthetase-Like 1- (OASL1-) Deficient Mice upon Cisplatin Chemotherapy and Radiotherapy |
| title_fullStr | Enhanced Antitumor Immune Response in 2′-5′ Oligoadenylate Synthetase-Like 1- (OASL1-) Deficient Mice upon Cisplatin Chemotherapy and Radiotherapy |
| title_full_unstemmed | Enhanced Antitumor Immune Response in 2′-5′ Oligoadenylate Synthetase-Like 1- (OASL1-) Deficient Mice upon Cisplatin Chemotherapy and Radiotherapy |
| title_short | Enhanced Antitumor Immune Response in 2′-5′ Oligoadenylate Synthetase-Like 1- (OASL1-) Deficient Mice upon Cisplatin Chemotherapy and Radiotherapy |
| title_sort | enhanced antitumor immune response in 2 5 oligoadenylate synthetase like 1 oasl1 deficient mice upon cisplatin chemotherapy and radiotherapy |
| url | http://dx.doi.org/10.1155/2019/7596786 |
| work_keys_str_mv | AT chankyusim enhancedantitumorimmuneresponsein25oligoadenylatesynthetaselike1oasl1deficientmiceuponcisplatinchemotherapyandradiotherapy AT junghoonlee enhancedantitumorimmuneresponsein25oligoadenylatesynthetaselike1oasl1deficientmiceuponcisplatinchemotherapyandradiotherapy AT injeoungbaek enhancedantitumorimmuneresponsein25oligoadenylatesynthetaselike1oasl1deficientmiceuponcisplatinchemotherapyandradiotherapy AT sangwooklee enhancedantitumorimmuneresponsein25oligoadenylatesynthetaselike1oasl1deficientmiceuponcisplatinchemotherapyandradiotherapy AT myeongsuplee enhancedantitumorimmuneresponsein25oligoadenylatesynthetaselike1oasl1deficientmiceuponcisplatinchemotherapyandradiotherapy |