Enhancing T-cell recruitment in renal cell carcinoma with cytokine-armed adenoviruses
Immunotherapy has emerged as a promising approach for cancer treatment, with oncolytic adenoviruses showing power as immunotherapeutic agents. In this study, we investigated the immunotherapeutic potential of an adenovirus construct expressing CXCL9, CXCL10, or IL-15 in clear cell renal cell carcino...
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| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2407532 |
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| author | Michaela Feodoroff Firas Hamdan Gabriella Antignani Sara Feola Manlio Fusciello Salvatore Russo Jacopo Chiaro Katja Välimäki Teijo Pellinen Rui M. Branca Janne Lehtiö Federica D´alessio Paolo Bottega Virpi Stigzelius Janita Sandberg Jonna Clancy Jukka Partanen Minna Malmstedt Antti Rannikko Vilja Pietiäinen Mikaela Grönholm Vincenzo Cerullo |
| author_facet | Michaela Feodoroff Firas Hamdan Gabriella Antignani Sara Feola Manlio Fusciello Salvatore Russo Jacopo Chiaro Katja Välimäki Teijo Pellinen Rui M. Branca Janne Lehtiö Federica D´alessio Paolo Bottega Virpi Stigzelius Janita Sandberg Jonna Clancy Jukka Partanen Minna Malmstedt Antti Rannikko Vilja Pietiäinen Mikaela Grönholm Vincenzo Cerullo |
| author_sort | Michaela Feodoroff |
| collection | DOAJ |
| description | Immunotherapy has emerged as a promising approach for cancer treatment, with oncolytic adenoviruses showing power as immunotherapeutic agents. In this study, we investigated the immunotherapeutic potential of an adenovirus construct expressing CXCL9, CXCL10, or IL-15 in clear cell renal cell carcinoma (ccRCC) tumor models. Our results demonstrated robust cytokine secretion upon viral treatment, suggesting effective transgene expression. Subsequent analysis using resistance-based transwell migration and microfluidic chip assays demonstrated increased T-cell migration in response to chemokine secretion by infected cells in both 2D and 3D cell models. Flow cytometry analysis revealed CXCR3 receptor expression across T-cell subsets, with the highest percentage found on CD8+ T-cells, underscoring their key role in immune cell migration. Alongside T-cells, we also detected NK-cells in the tumors of immunocompromised mice treated with cytokine-encoding adenoviruses. Furthermore, we identified potential immunogenic antigens that may enhance the efficacy and specificity of our armed oncolytic adenoviruses in ccRCC. Overall, our findings using ccRCC cell line, in vivo humanized mice, physiologically relevant PDCs in 2D and patient-derived organoids (PDOs) in 3D suggest that chemokine-armed adenoviruses hold promise for enhancing T-cell migration and improving immunotherapy outcomes in ccRCC. Our study contributes to the development of more effective ccRCC treatment strategies by elucidating immune cell infiltration and activation mechanisms within the tumor microenvironment (TME) and highlights the usefulness of PDOs for predicting clinical relevance and validating novel immunotherapeutic approaches. Overall, our research offers insights into the rational design and optimization of viral-based immunotherapies for ccRCC. |
| format | Article |
| id | doaj-art-9f9b01d5a4b141ec9e694bed2adb86b2 |
| institution | OA Journals |
| issn | 2162-402X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-9f9b01d5a4b141ec9e694bed2adb86b22025-08-20T02:38:26ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2024.2407532Enhancing T-cell recruitment in renal cell carcinoma with cytokine-armed adenovirusesMichaela Feodoroff0Firas Hamdan1Gabriella Antignani2Sara Feola3Manlio Fusciello4Salvatore Russo5Jacopo Chiaro6Katja Välimäki7Teijo Pellinen8Rui M. Branca9Janne Lehtiö10Federica D´alessio11Paolo Bottega12Virpi Stigzelius13Janita Sandberg14Jonna Clancy15Jukka Partanen16Minna Malmstedt17Antti Rannikko18Vilja Pietiäinen19Mikaela Grönholm20Vincenzo Cerullo21Laboratory of Immunovirotherapy, Drug Research Program, University of Helsinki Faculty of Pharmacy, Helsinki, FinlandLaboratory of Immunovirotherapy, Drug Research Program, University of Helsinki Faculty of Pharmacy, Helsinki, FinlandLaboratory of Immunovirotherapy, Drug Research Program, University of Helsinki Faculty of Pharmacy, Helsinki, FinlandLaboratory of Immunovirotherapy, Drug Research Program, University of Helsinki Faculty of Pharmacy, Helsinki, FinlandLaboratory of Immunovirotherapy, Drug Research Program, University of Helsinki Faculty of Pharmacy, Helsinki, FinlandLaboratory of Immunovirotherapy, Drug Research Program, University of Helsinki Faculty of Pharmacy, Helsinki, FinlandLaboratory of Immunovirotherapy, Drug Research Program, University of Helsinki Faculty of Pharmacy, Helsinki, FinlandInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute for Life Sciences (HiLIFE), University of Helsinki, Helsinki, FinlandInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute for Life Sciences (HiLIFE), University of Helsinki, Helsinki, FinlandScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, SwedenScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Solna, SwedenLaboratory of Immunovirotherapy, Drug Research Program, University of Helsinki Faculty of Pharmacy, Helsinki, FinlandLaboratory of Immunovirotherapy, Drug Research Program, University of Helsinki Faculty of Pharmacy, Helsinki, FinlandLaboratory of Immunovirotherapy, Drug Research Program, University of Helsinki Faculty of Pharmacy, Helsinki, FinlandLaboratory of Immunovirotherapy, Drug Research Program, University of Helsinki Faculty of Pharmacy, Helsinki, FinlandDepartment of Research and Development, Finnish Red Cross Blood Service, Helsinki, FinlandDepartment of Research and Development, Finnish Red Cross Blood Service, Helsinki, FinlandiCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, FinlandiCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, FinlandInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute for Life Sciences (HiLIFE), University of Helsinki, Helsinki, FinlandLaboratory of Immunovirotherapy, Drug Research Program, University of Helsinki Faculty of Pharmacy, Helsinki, FinlandLaboratory of Immunovirotherapy, Drug Research Program, University of Helsinki Faculty of Pharmacy, Helsinki, FinlandImmunotherapy has emerged as a promising approach for cancer treatment, with oncolytic adenoviruses showing power as immunotherapeutic agents. In this study, we investigated the immunotherapeutic potential of an adenovirus construct expressing CXCL9, CXCL10, or IL-15 in clear cell renal cell carcinoma (ccRCC) tumor models. Our results demonstrated robust cytokine secretion upon viral treatment, suggesting effective transgene expression. Subsequent analysis using resistance-based transwell migration and microfluidic chip assays demonstrated increased T-cell migration in response to chemokine secretion by infected cells in both 2D and 3D cell models. Flow cytometry analysis revealed CXCR3 receptor expression across T-cell subsets, with the highest percentage found on CD8+ T-cells, underscoring their key role in immune cell migration. Alongside T-cells, we also detected NK-cells in the tumors of immunocompromised mice treated with cytokine-encoding adenoviruses. Furthermore, we identified potential immunogenic antigens that may enhance the efficacy and specificity of our armed oncolytic adenoviruses in ccRCC. Overall, our findings using ccRCC cell line, in vivo humanized mice, physiologically relevant PDCs in 2D and patient-derived organoids (PDOs) in 3D suggest that chemokine-armed adenoviruses hold promise for enhancing T-cell migration and improving immunotherapy outcomes in ccRCC. Our study contributes to the development of more effective ccRCC treatment strategies by elucidating immune cell infiltration and activation mechanisms within the tumor microenvironment (TME) and highlights the usefulness of PDOs for predicting clinical relevance and validating novel immunotherapeutic approaches. Overall, our research offers insights into the rational design and optimization of viral-based immunotherapies for ccRCC.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2407532Cytokinesimmunotherapyoncolytic virusesrenal cell carcinomatumor peptides |
| spellingShingle | Michaela Feodoroff Firas Hamdan Gabriella Antignani Sara Feola Manlio Fusciello Salvatore Russo Jacopo Chiaro Katja Välimäki Teijo Pellinen Rui M. Branca Janne Lehtiö Federica D´alessio Paolo Bottega Virpi Stigzelius Janita Sandberg Jonna Clancy Jukka Partanen Minna Malmstedt Antti Rannikko Vilja Pietiäinen Mikaela Grönholm Vincenzo Cerullo Enhancing T-cell recruitment in renal cell carcinoma with cytokine-armed adenoviruses OncoImmunology Cytokines immunotherapy oncolytic viruses renal cell carcinoma tumor peptides |
| title | Enhancing T-cell recruitment in renal cell carcinoma with cytokine-armed adenoviruses |
| title_full | Enhancing T-cell recruitment in renal cell carcinoma with cytokine-armed adenoviruses |
| title_fullStr | Enhancing T-cell recruitment in renal cell carcinoma with cytokine-armed adenoviruses |
| title_full_unstemmed | Enhancing T-cell recruitment in renal cell carcinoma with cytokine-armed adenoviruses |
| title_short | Enhancing T-cell recruitment in renal cell carcinoma with cytokine-armed adenoviruses |
| title_sort | enhancing t cell recruitment in renal cell carcinoma with cytokine armed adenoviruses |
| topic | Cytokines immunotherapy oncolytic viruses renal cell carcinoma tumor peptides |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2407532 |
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