Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC model
IntroductionPancreatic ductal adenocarcinoma (PDAC) is largely refractory to cancer immunotherapy with PD-1 immune checkpoint blockade (ICB). Oncolytic virotherapy has been shown to synergize with ICB. In this work, we investigated the combination of anti-PD-1 and oncolytic measles vaccine in an imm...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1096162/full |
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| author | Rūta Veinalde Gemma Pidelaserra-Martí Gemma Pidelaserra-Martí Gemma Pidelaserra-Martí Coline Moulin Coline Moulin Chin Leng Tan Chin Leng Tan Theresa E. Schäfer Na Kang Claudia R. Ball Claudia R. Ball Jonas Leichsenring Jonas Leichsenring Albrecht Stenzinger Lars Kaderali Dirk Jäger Dirk Jäger Guy Ungerechts Guy Ungerechts Christine E. Engeland Christine E. Engeland Christine E. Engeland |
| author_facet | Rūta Veinalde Gemma Pidelaserra-Martí Gemma Pidelaserra-Martí Gemma Pidelaserra-Martí Coline Moulin Coline Moulin Chin Leng Tan Chin Leng Tan Theresa E. Schäfer Na Kang Claudia R. Ball Claudia R. Ball Jonas Leichsenring Jonas Leichsenring Albrecht Stenzinger Lars Kaderali Dirk Jäger Dirk Jäger Guy Ungerechts Guy Ungerechts Christine E. Engeland Christine E. Engeland Christine E. Engeland |
| author_sort | Rūta Veinalde |
| collection | DOAJ |
| description | IntroductionPancreatic ductal adenocarcinoma (PDAC) is largely refractory to cancer immunotherapy with PD-1 immune checkpoint blockade (ICB). Oncolytic virotherapy has been shown to synergize with ICB. In this work, we investigated the combination of anti-PD-1 and oncolytic measles vaccine in an immunocompetent transplantable PDAC mouse model.MethodsWe characterized tumor-infiltrating T cells by immunohistochemistry, flow cytometry and T cell receptor sequencing. Further, we performed gene expression profiling of tumor samples at baseline, after treatment, and when tumors progressed. Moreover, we analyzed systemic anti-tumor and anti-viral immunity.ResultsCombination treatment significantly prolonged survival compared to monotherapies. Tumor-infiltrating immune cells were increased after virotherapy. Gene expression profiling revealed a unique, but transient signature of immune activation after combination treatment. However, systemic anti-tumor immunity was induced by virotherapy and remained detectable even when tumors progressed. Anti-PD-1 treatment did not impact anti-viral immunity.DiscussionOur results indicate that combined virotherapy and ICB induces anti-tumor immunity and reshapes the tumor immune environment. However, further refinement of this approach may be required to develop its full potential and achieve durable efficacy. |
| first_indexed | 2024-04-10T22:42:03Z |
| format | Article |
| id | doaj.art-ba74acb47dae49da8309a7f9f1784388 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T22:42:03Z |
| publishDate | 2023-01-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-ba74acb47dae49da8309a7f9f17843882023-01-16T04:48:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011310.3389/fimmu.2022.10961621096162Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC modelRūta Veinalde0Gemma Pidelaserra-Martí1Gemma Pidelaserra-Martí2Gemma Pidelaserra-Martí3Coline Moulin4Coline Moulin5Chin Leng Tan6Chin Leng Tan7Theresa E. Schäfer8Na Kang9Claudia R. Ball10Claudia R. Ball11Jonas Leichsenring12Jonas Leichsenring13Albrecht Stenzinger14Lars Kaderali15Dirk Jäger16Dirk Jäger17Guy Ungerechts18Guy Ungerechts19Christine E. Engeland20Christine E. Engeland21Christine E. Engeland22Clinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Heidelberg, GermanyClinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Heidelberg, GermanyFaculty of Health, School of Medicine, Center for Biomedical Research and Education (ZBAF), Institute of Virology and Microbiology, Witten/Herdecke University, Witten, GermanyFaculty of Biosciences, Heidelberg University, Heidelberg, GermanyFaculty of Health, School of Medicine, Center for Biomedical Research and Education (ZBAF), Institute of Virology and Microbiology, Witten/Herdecke University, Witten, GermanyEcole Normale Supérieure de Lyon, Lyon, FranceFaculty of Biosciences, Heidelberg University, Heidelberg, GermanyClinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, GermanyClinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Translational Medical Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Translational Medical Oncology, National Center for Tumor Diseases Dresden (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, GermanyCenter for Personalized Oncology, National Center for Tumor Diseases (NCT) Dresden and University Hospital Carl Gustav Carus, Faculty of Medicine and Technische Universität Dresden, Dresden, GermanyInstitute of Pathology, Heidelberg University Hospital, Heidelberg, Germany0Institut für Pathologie, Zytologie und molekulare Diagnostik, Regiomed Klinikum Coburg, Coburg, GermanyInstitute of Pathology, Heidelberg University Hospital, Heidelberg, Germany1Institute for Bioinformatics, University Medicine Greifswald, Greifswald, Germany2Clinical Cooperation Unit Applied Tumor Immunity, German Cancer Research Center (DKFZ), Heidelberg, Germany3Department of Medical Oncology, University Hospital Heidelberg, Heidelberg, Germany and National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, GermanyClinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Heidelberg, Germany3Department of Medical Oncology, University Hospital Heidelberg, Heidelberg, Germany and National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, GermanyClinical Cooperation Unit Virotherapy, German Cancer Research Center (DKFZ), Heidelberg, GermanyFaculty of Health, School of Medicine, Center for Biomedical Research and Education (ZBAF), Institute of Virology and Microbiology, Witten/Herdecke University, Witten, Germany3Department of Medical Oncology, University Hospital Heidelberg, Heidelberg, Germany and National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, GermanyIntroductionPancreatic ductal adenocarcinoma (PDAC) is largely refractory to cancer immunotherapy with PD-1 immune checkpoint blockade (ICB). Oncolytic virotherapy has been shown to synergize with ICB. In this work, we investigated the combination of anti-PD-1 and oncolytic measles vaccine in an immunocompetent transplantable PDAC mouse model.MethodsWe characterized tumor-infiltrating T cells by immunohistochemistry, flow cytometry and T cell receptor sequencing. Further, we performed gene expression profiling of tumor samples at baseline, after treatment, and when tumors progressed. Moreover, we analyzed systemic anti-tumor and anti-viral immunity.ResultsCombination treatment significantly prolonged survival compared to monotherapies. Tumor-infiltrating immune cells were increased after virotherapy. Gene expression profiling revealed a unique, but transient signature of immune activation after combination treatment. However, systemic anti-tumor immunity was induced by virotherapy and remained detectable even when tumors progressed. Anti-PD-1 treatment did not impact anti-viral immunity.DiscussionOur results indicate that combined virotherapy and ICB induces anti-tumor immunity and reshapes the tumor immune environment. However, further refinement of this approach may be required to develop its full potential and achieve durable efficacy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1096162/fullcancer immunotherapyimmune checkpointPD-1oncolytic virusmeasles vaccinePDAC |
| spellingShingle | Rūta Veinalde Gemma Pidelaserra-Martí Gemma Pidelaserra-Martí Gemma Pidelaserra-Martí Coline Moulin Coline Moulin Chin Leng Tan Chin Leng Tan Theresa E. Schäfer Na Kang Claudia R. Ball Claudia R. Ball Jonas Leichsenring Jonas Leichsenring Albrecht Stenzinger Lars Kaderali Dirk Jäger Dirk Jäger Guy Ungerechts Guy Ungerechts Christine E. Engeland Christine E. Engeland Christine E. Engeland Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC model Frontiers in Immunology cancer immunotherapy immune checkpoint PD-1 oncolytic virus measles vaccine PDAC |
| title | Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC model |
| title_full | Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC model |
| title_fullStr | Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC model |
| title_full_unstemmed | Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC model |
| title_short | Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC model |
| title_sort | virotherapy combined with anti pd 1 transiently reshapes the tumor immune environment and induces anti tumor immunity in a preclinical pdac model |
| topic | cancer immunotherapy immune checkpoint PD-1 oncolytic virus measles vaccine PDAC |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1096162/full |
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