Genetically Engineered Probiotic <i>Limosilactobacillus reuteri</i> Releasing IL-22 (LR-IL-22) Modifies the Tumor Microenvironment, Enabling Irradiation in Ovarian Cancer
Despite recent advances in cancer therapy, ovarian cancer remains the most lethal gynecological cancer worldwide, making it crucial and of the utmost importance to establish novel therapeutic strategies. Adjuvant radiotherapy has been assessed historically, but its use was limited by intestinal toxi...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/3/474 |
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| author | Diala F. Hamade Michael W. Epperly Renee Fisher Wen Hou Donna Shields Jan-Peter van Pijkeren Brian J. Leibowitz Lan G. Coffman Hong Wang M. Saiful Huq Ziyu Huang Claude J. Rogers Anda M. Vlad Joel S. Greenberger Amitava Mukherjee |
| author_facet | Diala F. Hamade Michael W. Epperly Renee Fisher Wen Hou Donna Shields Jan-Peter van Pijkeren Brian J. Leibowitz Lan G. Coffman Hong Wang M. Saiful Huq Ziyu Huang Claude J. Rogers Anda M. Vlad Joel S. Greenberger Amitava Mukherjee |
| author_sort | Diala F. Hamade |
| collection | DOAJ |
| description | Despite recent advances in cancer therapy, ovarian cancer remains the most lethal gynecological cancer worldwide, making it crucial and of the utmost importance to establish novel therapeutic strategies. Adjuvant radiotherapy has been assessed historically, but its use was limited by intestinal toxicity. We recently established the role of <i>Limosilactobacillus reuteri</i> 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. |
| first_indexed | 2024-03-08T04:01:07Z |
| format | Article |
| id | doaj.art-f567c6c83dde4f999e7419fd73b9be68 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-08T04:01:07Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f567c6c83dde4f999e7419fd73b9be682024-02-09T15:08:39ZengMDPI AGCancers2072-66942024-01-0116347410.3390/cancers16030474Genetically Engineered Probiotic <i>Limosilactobacillus reuteri</i> Releasing IL-22 (LR-IL-22) Modifies the Tumor Microenvironment, Enabling Irradiation in Ovarian CancerDiala F. Hamade0Michael W. Epperly1Renee Fisher2Wen Hou3Donna Shields4Jan-Peter van Pijkeren5Brian J. Leibowitz6Lan G. Coffman7Hong Wang8M. Saiful Huq9Ziyu Huang10Claude J. Rogers11Anda M. Vlad12Joel S. Greenberger13Amitava Mukherjee14Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USADepartment of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USADepartment of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USADepartment of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USADepartment of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USADepartment of Food Science, University of Wisconsin-Madison, Madison, WI 53706, USADepartment of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USADepartment of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USADepartment of Biostatistics, University of Pittsburgh, Pittsburgh, PA 15260, USADepartment of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USADepartment of Biostatistics, University of Pittsburgh, Pittsburgh, PA 15260, USAChromoLogic, LLC, Monrovia, CA 91016, USADivision of Cancer Prevention, National Cancer Institute, Rockville, MD 20850, USADepartment of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USADepartment of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USADespite recent advances in cancer therapy, ovarian cancer remains the most lethal gynecological cancer worldwide, making it crucial and of the utmost importance to establish novel therapeutic strategies. Adjuvant radiotherapy has been assessed historically, but its use was limited by intestinal toxicity. We recently established the role of <i>Limosilactobacillus reuteri</i> 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.https://www.mdpi.com/2072-6694/16/3/474genetically engineeredprobiotic<i>Limosilactobacillus reuteri</i> |
| spellingShingle | Diala F. Hamade Michael W. Epperly Renee Fisher Wen Hou Donna Shields Jan-Peter van Pijkeren Brian J. Leibowitz Lan G. Coffman Hong Wang M. Saiful Huq Ziyu Huang Claude J. Rogers Anda M. Vlad Joel S. Greenberger Amitava Mukherjee Genetically Engineered Probiotic <i>Limosilactobacillus reuteri</i> Releasing IL-22 (LR-IL-22) Modifies the Tumor Microenvironment, Enabling Irradiation in Ovarian Cancer Cancers genetically engineered probiotic <i>Limosilactobacillus reuteri</i> |
| title | Genetically Engineered Probiotic <i>Limosilactobacillus reuteri</i> Releasing IL-22 (LR-IL-22) Modifies the Tumor Microenvironment, Enabling Irradiation in Ovarian Cancer |
| title_full | Genetically Engineered Probiotic <i>Limosilactobacillus reuteri</i> Releasing IL-22 (LR-IL-22) Modifies the Tumor Microenvironment, Enabling Irradiation in Ovarian Cancer |
| title_fullStr | Genetically Engineered Probiotic <i>Limosilactobacillus reuteri</i> Releasing IL-22 (LR-IL-22) Modifies the Tumor Microenvironment, Enabling Irradiation in Ovarian Cancer |
| title_full_unstemmed | Genetically Engineered Probiotic <i>Limosilactobacillus reuteri</i> Releasing IL-22 (LR-IL-22) Modifies the Tumor Microenvironment, Enabling Irradiation in Ovarian Cancer |
| title_short | Genetically Engineered Probiotic <i>Limosilactobacillus reuteri</i> Releasing IL-22 (LR-IL-22) Modifies the Tumor Microenvironment, Enabling Irradiation in Ovarian Cancer |
| title_sort | genetically engineered probiotic i limosilactobacillus reuteri i releasing il 22 lr il 22 modifies the tumor microenvironment enabling irradiation in ovarian cancer |
| topic | genetically engineered probiotic <i>Limosilactobacillus reuteri</i> |
| url | https://www.mdpi.com/2072-6694/16/3/474 |
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