Recombinant immunotoxin induces tumor intrinsic STING signaling against head and neck squamous cell carcinoma
Abstract The innate immune stimulator of interferon genes (STING) pathway is known to activate type I interferons (IFN-I) and participate in generating antitumor immunity. We previously produced hDT806, a recombinant diphtheria immunotoxin, and demonstrated its efficacy against head and neck squamou...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-45797-7 |
| _version_ | 1797647325323067392 |
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| author | Guiqin Xie Liang Shan Cuicui Yang Yuanyi Liu Xiaowu Pang Shaolei Teng Tzyy-Choou Wu Xinbin Gu |
| author_facet | Guiqin Xie Liang Shan Cuicui Yang Yuanyi Liu Xiaowu Pang Shaolei Teng Tzyy-Choou Wu Xinbin Gu |
| author_sort | Guiqin Xie |
| collection | DOAJ |
| description | Abstract The innate immune stimulator of interferon genes (STING) pathway is known to activate type I interferons (IFN-I) and participate in generating antitumor immunity. We previously produced hDT806, a recombinant diphtheria immunotoxin, and demonstrated its efficacy against head and neck squamous cell carcinoma (HNSCC). However, it’s unknown whether the tumor-intrinsic STING plays a role in the anti-HNSCC effects of hDT806. In this study, we investigated the innate immune modulation of hDT806 on HNSCC. hDT806 significantly upregulated the level of STING and the ratio of p-TBK1/TBK1 in the HNSCC cells. Moreover, intratumoral hDT806 treatment increased the expression of STING-IFN-I signaling proteins including IFNA1, IFNB, CXCL10 and MX1, a marker of IFN-I receptor activity, in the HNSCC xenografts. Overexpression of STING mimicked the hDT806-induced upregulation of the STING-IFN-I signaling and induced apoptosis in the HNSCC cells. In the mouse xenograft models of HNSCC with STING overexpression, we observed a significant suppression of tumor growth and reduced tumor weight with increased apoptosis compared to their control xenograft counterparts without STING overexpression. Collectively, our data revealed that hDT806 may act as a stimulator of tumor-intrinsic STING-IFN-I signaling to inhibit tumor growth in HNSCC. |
| first_indexed | 2024-03-11T15:14:39Z |
| format | Article |
| id | doaj.art-4c29c2a9b100442dad3224f3dddb2da3 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-11T15:14:39Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-4c29c2a9b100442dad3224f3dddb2da32023-10-29T12:20:17ZengNature PortfolioScientific Reports2045-23222023-10-0113111310.1038/s41598-023-45797-7Recombinant immunotoxin induces tumor intrinsic STING signaling against head and neck squamous cell carcinomaGuiqin Xie0Liang Shan1Cuicui Yang2Yuanyi Liu3Xiaowu Pang4Shaolei Teng5Tzyy-Choou Wu6Xinbin Gu7Department of Oral Pathology, Howard UniversityCancer Center, Howard UniversityDepartment of Oral Pathology, Howard UniversityAngimmune LLCDepartment of Oral Pathology, Howard UniversityDepartment of Biology, Howard UniversityPathology, Oncology, Obstetrics and Gynecology, and Molecular Microbiology and Immunology, Johns Hopkins University School of MedicineDepartment of Oral Pathology, Howard UniversityAbstract The innate immune stimulator of interferon genes (STING) pathway is known to activate type I interferons (IFN-I) and participate in generating antitumor immunity. We previously produced hDT806, a recombinant diphtheria immunotoxin, and demonstrated its efficacy against head and neck squamous cell carcinoma (HNSCC). However, it’s unknown whether the tumor-intrinsic STING plays a role in the anti-HNSCC effects of hDT806. In this study, we investigated the innate immune modulation of hDT806 on HNSCC. hDT806 significantly upregulated the level of STING and the ratio of p-TBK1/TBK1 in the HNSCC cells. Moreover, intratumoral hDT806 treatment increased the expression of STING-IFN-I signaling proteins including IFNA1, IFNB, CXCL10 and MX1, a marker of IFN-I receptor activity, in the HNSCC xenografts. Overexpression of STING mimicked the hDT806-induced upregulation of the STING-IFN-I signaling and induced apoptosis in the HNSCC cells. In the mouse xenograft models of HNSCC with STING overexpression, we observed a significant suppression of tumor growth and reduced tumor weight with increased apoptosis compared to their control xenograft counterparts without STING overexpression. Collectively, our data revealed that hDT806 may act as a stimulator of tumor-intrinsic STING-IFN-I signaling to inhibit tumor growth in HNSCC.https://doi.org/10.1038/s41598-023-45797-7 |
| spellingShingle | Guiqin Xie Liang Shan Cuicui Yang Yuanyi Liu Xiaowu Pang Shaolei Teng Tzyy-Choou Wu Xinbin Gu Recombinant immunotoxin induces tumor intrinsic STING signaling against head and neck squamous cell carcinoma Scientific Reports |
| title | Recombinant immunotoxin induces tumor intrinsic STING signaling against head and neck squamous cell carcinoma |
| title_full | Recombinant immunotoxin induces tumor intrinsic STING signaling against head and neck squamous cell carcinoma |
| title_fullStr | Recombinant immunotoxin induces tumor intrinsic STING signaling against head and neck squamous cell carcinoma |
| title_full_unstemmed | Recombinant immunotoxin induces tumor intrinsic STING signaling against head and neck squamous cell carcinoma |
| title_short | Recombinant immunotoxin induces tumor intrinsic STING signaling against head and neck squamous cell carcinoma |
| title_sort | recombinant immunotoxin induces tumor intrinsic sting signaling against head and neck squamous cell carcinoma |
| url | https://doi.org/10.1038/s41598-023-45797-7 |
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