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Genetically Engineered Probiotic Limosilactobacillus reuteri Releasing IL-22 (LR-IL-22) Modifies the Tumor Microenvironment, Enabling Irradiation in Ovarian Cancer.
Hamade, Diala F; Epperly, Michael W; Fisher, Renee; Hou, Wen; Shields, Donna; van Pijkeren, Jan-Peter; Leibowitz, Brian J; Coffman, Lan G; Wang, Hong; Huq, M Saiful; Huang, Ziyu; Rogers, Claude J; Vlad, Anda M; Greenberger, Joel S; Mukherjee, Amitava.
Afiliación
  • Hamade DF; Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA.
  • Epperly MW; Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA.
  • Fisher R; Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA.
  • Hou W; Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA.
  • Shields D; Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA.
  • van Pijkeren JP; Department of Food Science, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • Leibowitz BJ; Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA.
  • Coffman LG; Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
  • Wang H; Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA 15260, USA.
  • Huq MS; Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA.
  • Huang Z; Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA 15260, USA.
  • Rogers CJ; ChromoLogic, LLC, Monrovia, CA 91016, USA.
  • Vlad AM; Division of Cancer Prevention, National Cancer Institute, Rockville, MD 20850, USA.
  • Greenberger JS; Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA.
  • Mukherjee A; Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA.
Cancers (Basel) ; 16(3)2024 Jan 23.
Article en En | MEDLINE | ID: mdl-38339228
ABSTRACT
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 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Guideline / Prognostic_studies Aspecto: Patient_preference Idioma: En Revista: Cancers (Basel) Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Guideline / Prognostic_studies Aspecto: Patient_preference Idioma: En Revista: Cancers (Basel) Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza