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Adjuvant radiotherapy has been assessed historically, but its use was limited by intestinal toxicity. We recently established the role of Limosilactobacillus reuteri in releasing IL-22 (LR-IL-22) as an effective radiation mitigator, and we have now assessed its effect in an ovarian cancer mouse model. We hypothesized that an LR-IL-22 gavage would enable intestinal radioprotection by modifying the tumor microenvironment and, subsequently, improving overall survival in female C57BL\/6MUC-1 mice with widespread abdominal syngeneic 2F8cis ovarian cancer. Herein, we report that the LR-IL-22 gavage not only improved overall survival in mice when combined with a PD-L1 inhibitor by inducing differential gene expression in irradiated stem cells but also induced PD-L1 protein expression in ovarian cancer cells and mobilized CD8+ T cells in whole abdomen irradiated mice. The addition of LR-IL-22 to a combined treatment modality with fractionated whole abdomen radiation (WAI) and systemic chemotherapy and immunotherapy regimens can facilitate a safe and effective protocol to reduce tumor burden, increase survival, and improve the quality of life of a locally advanced ovarian cancer patient.<\/jats:p>","DOI":"10.3390\/cancers16030474","type":"journal-article","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T07:22:32Z","timestamp":1705994552000},"page":"474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Genetically Engineered Probiotic Limosilactobacillus reuteri Releasing IL-22 (LR-IL-22) Modifies the Tumor Microenvironment, Enabling Irradiation in Ovarian Cancer"],"prefix":"10.3390","volume":"16","author":[{"given":"Diala F.","family":"Hamade","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Epperly","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Shields","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Peter","family":"van Pijkeren","sequence":"additional","affiliation":[{"name":"Department of Food Science, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Leibowitz","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan G.","family":"Coffman","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Saiful","family":"Huq","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude J.","family":"Rogers","sequence":"additional","affiliation":[{"name":"ChromoLogic, LLC, Monrovia, CA 91016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5266-9695","authenticated-orcid":false,"given":"Anda M.","family":"Vlad","sequence":"additional","affiliation":[{"name":"Division of Cancer Prevention, National Cancer Institute, Rockville, MD 20850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2271-7566","authenticated-orcid":false,"given":"Joel S.","family":"Greenberger","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5603-5147","authenticated-orcid":false,"given":"Amitava","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3389\/fonc.2017.00177","article-title":"Radiation Treatment in Women with Ovarian Cancer: Past, Present, and Future","volume":"7","author":"Fields","year":"2017","journal-title":"Front. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/0360-3016(92)90777-F","article-title":"Epithelial ovarian cancer: The role of radiotherapy","volume":"22","author":"Dembo","year":"1992","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/0090-8258(90)90377-W","article-title":"Palliative benefit of radiation therapy in advanced ovarian cancer","volume":"37","author":"May","year":"1990","journal-title":"Gynecol. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/S0360-3016(00)00446-6","article-title":"A phase I\/II study of hypofractionated whole abdominal radiation therapy in patients with chemorsesistant ovarian carcinoma: Karnofsky score determines treatment outcome","volume":"47","author":"Faul","year":"2000","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1667\/RADE-21-00224.1","article-title":"Lactobacillus reuteri Releasing IL-22 (LR-IL-22) Facilitates Intestinal Radioprotection for Whole-Abdomen Irradiation (WAI) of Ovarian Cancer","volume":"198","author":"Hamade","year":"2022","journal-title":"Radiat. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3664","DOI":"10.1038\/onc.2012.397","article-title":"Immunobiology of human mucin 1 in a preclinical ovarian tumor model","volume":"32","author":"Budiu","year":"2013","journal-title":"Oncogene"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1007\/s00262-015-1712-6","article-title":"Anti-PD-L1 prolongs survival and triggers T cell but not humoral anti-tumor immune responses in a human MUC1- expressing preclinical ovarian cancer model","volume":"64","author":"Mony","year":"2015","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1046\/j.1525-1438.1993.03010024.x","article-title":"Testing the validity of a prognostic classification in patients with surgically optimal ovarian carcinoma: A 15-year review","volume":"3","author":"Carey","year":"1993","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1667\/RR15486.1","article-title":"Anti-ferroptosis drug, Baicalein, enhances total body irradiation mitigation by two other drugs that target apoptosis and necroptosis","volume":"193","author":"Thermozier","year":"2020","journal-title":"Radiat. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.21873\/invivo.11743","article-title":"Second-generation probiotics producing IL-22 increase survival of mice after total body irradiation","volume":"34","author":"Zhang","year":"2020","journal-title":"In Vivo"},{"key":"ref_11","first-page":"9","article-title":"Emerging Roles of 5-Lipoxygenase Phosphorylation in Inflammation and Cell Death","volume":"29","author":"Sun","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"919567","DOI":"10.3389\/fphar.2022.919567","article-title":"Caspase-4 and -5 Biology in the Pathogenesis of Inflammatory Bowel Disease","volume":"31","author":"Smith","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"805018","DOI":"10.3389\/fimmu.2022.805018","article-title":"Protein O-GlcNAcylation Regulates Innate Immune Cell Function","volume":"13","author":"Dong","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"338","DOI":"10.2164\/jandrol.107.003558","article-title":"Phosphorylation of Mitogen-Activated Protein Kinase 8 (MAPK8) Is Associated with Germ Cell Apoptosis and Redistribution of the Bcl2-Modifying Factor (BMF)","volume":"29","author":"Show","year":"2008","journal-title":"J. Androl."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1158\/0008-5472.CAN-13-1275","article-title":"LIMD2 is a small LIM-only protein overexpressed in metastatic lesions that regulates cell motility and tumor progression by directly binding to and activating the integrin-linked kinase","volume":"74","author":"Peng","year":"2014","journal-title":"Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"216225","DOI":"10.1016\/j.canlet.2023.216225","article-title":"Regulatory network and targeted interventions for CCDC family in tumor pathogenesis","volume":"565","author":"Liu","year":"2023","journal-title":"Cancer Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1038\/onc.2017.287","article-title":"KCTD12 promotes tumorigenesis by facilitating CDC25B\/CDK1\/Aurora A-dependent G2\/M transition","volume":"36","author":"Zhong","year":"2017","journal-title":"Oncogene"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/cam4.1812","article-title":"CCNG1 (Cyclin G1) regulation by mutant-P53 via induction of Notch3 expression promotes high-grade serous ovarian cancer (HGSOC) tumorigenesis and progression","volume":"8","author":"Xu","year":"2019","journal-title":"Cancer Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e22777","DOI":"10.1097\/MD.0000000000022777","article-title":"Comprehensive analysis of the expression and prognosis for S100 in human ovarian cancer: A STROBE study","volume":"99","author":"Xu","year":"2020","journal-title":"Medicine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1038\/bjc.2014.169","article-title":"Proteomics analysis of melanoma metastases: Association between S100A13 expression and chemotherapy resistance","volume":"110","author":"Azimi","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Birkenkamp-Demtr\u00f6der, K., Hahn, S.A., Mansilla, F., Thorsen, K., Maghnouj, A., Christensen, R., Oster, B., and Orntoft, T.F. (2013). Keratin23 (KRT23) knockdown decreases proliferation and affects the DNA damage response of colon cancer cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073593"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s12935-019-0780-7","article-title":"Stimulative role of ST6GALNAC1 in proliferation, migration and invasion of ovarian cancer stem cells via the Akt signaling pathway","volume":"1986","author":"Wang","year":"2019","journal-title":"Cancer Cell. Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"36850421997273","DOI":"10.1177\/0036850421997273","article-title":"A review of the mechanism of DDIT4 serve as a mitochondrial related protein in tumor regulation","volume":"104","author":"Ding","year":"2021","journal-title":"Sci. Prog."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"956225","DOI":"10.3389\/fonc.2022.956225","article-title":"Polo-Like Kinase 2: From Principle to Practice","volume":"12","author":"Zhang","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.3892\/etm.2015.2257","article-title":"Knockdown of S100A11 expression suppresses ovarian cancer cell growth and invasion","volume":"9","author":"Liu","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/j.1349-7006.2011.02108.x","article-title":"Transforming growth factor-\u03b2-stimulated clone-22 is a negative-feedback regulator of Ras\/Raf signaling: Implications for tumorigenesis","volume":"103","author":"Nakamura","year":"2012","journal-title":"Cancer Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Sinkala, M., Nkhoma, P., Mulder, N., and Martin, D.P. (2021). Integrated molecular characterisation of the MAPK pathways in human cancers reveals pharmacologically vulnerable mutations and gene dependencies. Commun. Biol., 4.","DOI":"10.1038\/s42003-020-01552-6"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"309","DOI":"10.2478\/s11658-012-0012-9","article-title":"Deficiency in TR4 nuclear receptor abrogates Gadd45a expression and increases cytotoxicity induced by ionizing radiation","volume":"17","author":"Yan","year":"2012","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"40032","DOI":"10.1074\/jbc.M506510200","article-title":"Disruption of the phosphatidylserine decarboxylase gene in mice causes embryonic lethality and mitochondrial defects","volume":"280","author":"Steenbergen","year":"2005","journal-title":"Chem. Biol. Chem."},{"key":"ref_30","first-page":"5830","article-title":"Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases","volume":"59","author":"Zhong","year":"1999","journal-title":"Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S0002-9440(10)64554-3","article-title":"The Expression and Distribution of the Hypoxia-Inducible Factors HIF-1\u03b1 and HIF-2\u03b1 in Normal Human Tissues, Cancers, and Tumor-Associated Macrophages","volume":"157","author":"Talks","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.ygyno.2010.10.018","article-title":"Low-dose abdominal radiation as a docetaxel chemosensitizer for recurrent epithelial ovarian cancer: A phase 1 study of the Gynecologic Oncology Group","volume":"120","author":"Kunos","year":"2011","journal-title":"Gynecol. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.ijrobp.2020.09.059","article-title":"Phase I study of low-dose fractionated whole abdominal radiation therapy in combination with weekly paclitaxel for platinum-resistant ovarian cancer (GCGS-01)","volume":"109","author":"Ngoi","year":"2021","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1186\/s13014-019-1381-2","article-title":"Adjuvant intensity modulated whole-abdominal radiation therapy for high-risk patients with ovarian cancer FIGO stage III: Final results of a prospective phase 2 study","volume":"14","author":"Arians","year":"2019","journal-title":"Radiat. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.urolonc.2016.01.006","article-title":"Blocking immune checkpoints in prostate, kidney, and urothelial cancer: An overview","volume":"34","author":"Alme","year":"2016","journal-title":"Urol. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"18538","DOI":"10.1073\/pnas.0509182102","article-title":"Intraepithelial CD81 tumor-infiltrating lymphocytes and a high CD81\/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer","volume":"102","author":"Sato","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.ygyno.2011.09.039","article-title":"Prognostic significance of tumor-infiltrating T cells in ovarian cancer: A meta-analysis","volume":"124","author":"Hwang","year":"2012","journal-title":"Gynecol. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4616","DOI":"10.1002\/cncr.32520","article-title":"Immunotherapy with checkpoint inhibitors in patients with ovarian cancer: Still promising?","volume":"125","year":"2019","journal-title":"Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1200\/JCO.19.02059","article-title":"Randomized Phase II trial of Nivolumab versus Nivolumab and Ipilimumab for recurrent or persistent Ovarian cancer: An NRG Oncology Study","volume":"38","author":"Zamarin","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1073\/pnas.0611533104","article-title":"Programmed cell death 1 ligand 1 and tumor infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer","volume":"104","author":"Hamanishi","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.ygyno.2019.05.021","article-title":"Safety, clinical activity, and biomarker assessments of atezolizumab from a Phase I study in advanced\/recurrent ovarian and uterine cancers","volume":"154","author":"Liu","year":"2019","journal-title":"Gynecol. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1001\/jamaoncol.2018.6258","article-title":"Efficacy and safety of avelumab for patients with recurrent or refractory ovarian cancer: Phase 1b results from the JAVELIN solid tumor trial","volume":"5","author":"Disis","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1200\/JCO.2016.72.1340","article-title":"Safety and clinical activity of the programmed death-ligand 1 inhibitor Durvalumab in combination with poly (ADP-Ribose) polymerase inhibitor Olaparib or vascular endothelial growth factor receptor 1-3 inhibitor Cediranib in women\u2019s cancers: A dose-escalation, Phase I Study","volume":"35","author":"Lee","year":"2017","journal-title":"J. Clin. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/3\/474\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:47:40Z","timestamp":1760104060000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/3\/474"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,23]]},"references-count":43,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["cancers16030474"],"URL":"https:\/\/doi.org\/10.3390\/cancers16030474","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,23]]}}}