Co-targeting of VEGFR2 and PD-L1 promotes survival and vasculature normalization in pleural mesothelioma
Pleural mesothelioma (PM) is an aggressive cancer caused by asbestos exposure, with limited treatment options and poor prognosis, highlighting the need for more effective therapies. Combining immune checkpoint blockade with anti-angiogenic therapy has shown potential in other cancers. Our study inve...
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2512104 |
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| author | Sophie Rovers Jonas Van Audenaerde Ruben Verloy Jorrit De Waele Louize Brants Christophe Hermans Ho Wa Lau Céline Merlin Maria Möller Ribas Peter Ponsaerts Steven Van Laere Filip Lardon An Wouters Scott A. Fisher Jan van Meerbeeck Elly Marcq Evelien Smits |
| author_facet | Sophie Rovers Jonas Van Audenaerde Ruben Verloy Jorrit De Waele Louize Brants Christophe Hermans Ho Wa Lau Céline Merlin Maria Möller Ribas Peter Ponsaerts Steven Van Laere Filip Lardon An Wouters Scott A. Fisher Jan van Meerbeeck Elly Marcq Evelien Smits |
| author_sort | Sophie Rovers |
| collection | DOAJ |
| description | Pleural mesothelioma (PM) is an aggressive cancer caused by asbestos exposure, with limited treatment options and poor prognosis, highlighting the need for more effective therapies. Combining immune checkpoint blockade with anti-angiogenic therapy has shown potential in other cancers. Our study investigated the combined inhibition of PD-L1 and VEGFR2 in a mouse model of PM. Using C57BL/6 mice with subcutaneous AE17 mesothelioma tumors, we assessed the effects of anti-PD-L1 therapy with induction, concomitant, or consolidation anti-VEGFR2 treatment. Mice received intraperitoneal doses every three days for three treatments. Tumor growth, survival, tumor-infiltrating immune cells and intra-tumoral vasculature were analyzed. Results demonstrated that combining anti-PD-L1 with induction or concomitant anti-VEGFR2 significantly delayed tumor growth, improved survival, and promoted vascular maturation. Flow cytometry suggested T cell exhaustion in monotherapy groups, while no significant changes were seen with concomitant treatment. Depleting CD4+ T cells reversed the positive effects of concomitant treatment. These findings suggest that dual inhibition of PD-L1 and VEGFR2 is a promising therapeutic approach for PM, with CD4+ T cells playing a critical role in the immune response. This dual targeting of immune checkpoints and angiogenesis offers a potential new avenue for improving outcomes in PM treatment and warrants further clinical exploration. |
| format | Article |
| id | doaj-art-3e7fdfdaa31b4378addd349a7f064a43 |
| institution | OA Journals |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-3e7fdfdaa31b4378addd349a7f064a432025-08-20T02:10:29ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2512104Co-targeting of VEGFR2 and PD-L1 promotes survival and vasculature normalization in pleural mesotheliomaSophie Rovers0Jonas Van Audenaerde1Ruben Verloy2Jorrit De Waele3Louize Brants4Christophe Hermans5Ho Wa Lau6Céline Merlin7Maria Möller Ribas8Peter Ponsaerts9Steven Van Laere10Filip Lardon11An Wouters12Scott A. Fisher13Jan van Meerbeeck14Elly Marcq15Evelien Smits16Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, BelgiumLaboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, BelgiumInstitute for Respiratory Health, National Centre for Asbestos Related Diseases (NCARD), University of Western Australia, Perth, AustraliaCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, BelgiumCenter for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, BelgiumPleural mesothelioma (PM) is an aggressive cancer caused by asbestos exposure, with limited treatment options and poor prognosis, highlighting the need for more effective therapies. Combining immune checkpoint blockade with anti-angiogenic therapy has shown potential in other cancers. Our study investigated the combined inhibition of PD-L1 and VEGFR2 in a mouse model of PM. Using C57BL/6 mice with subcutaneous AE17 mesothelioma tumors, we assessed the effects of anti-PD-L1 therapy with induction, concomitant, or consolidation anti-VEGFR2 treatment. Mice received intraperitoneal doses every three days for three treatments. Tumor growth, survival, tumor-infiltrating immune cells and intra-tumoral vasculature were analyzed. Results demonstrated that combining anti-PD-L1 with induction or concomitant anti-VEGFR2 significantly delayed tumor growth, improved survival, and promoted vascular maturation. Flow cytometry suggested T cell exhaustion in monotherapy groups, while no significant changes were seen with concomitant treatment. Depleting CD4+ T cells reversed the positive effects of concomitant treatment. These findings suggest that dual inhibition of PD-L1 and VEGFR2 is a promising therapeutic approach for PM, with CD4+ T cells playing a critical role in the immune response. This dual targeting of immune checkpoints and angiogenesis offers a potential new avenue for improving outcomes in PM treatment and warrants further clinical exploration.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2512104Anti-angiogenesiscancer immunotherapycombination therapyimmune checkpoint blockadepleural mesothelioma |
| spellingShingle | Sophie Rovers Jonas Van Audenaerde Ruben Verloy Jorrit De Waele Louize Brants Christophe Hermans Ho Wa Lau Céline Merlin Maria Möller Ribas Peter Ponsaerts Steven Van Laere Filip Lardon An Wouters Scott A. Fisher Jan van Meerbeeck Elly Marcq Evelien Smits Co-targeting of VEGFR2 and PD-L1 promotes survival and vasculature normalization in pleural mesothelioma OncoImmunology Anti-angiogenesis cancer immunotherapy combination therapy immune checkpoint blockade pleural mesothelioma |
| title | Co-targeting of VEGFR2 and PD-L1 promotes survival and vasculature normalization in pleural mesothelioma |
| title_full | Co-targeting of VEGFR2 and PD-L1 promotes survival and vasculature normalization in pleural mesothelioma |
| title_fullStr | Co-targeting of VEGFR2 and PD-L1 promotes survival and vasculature normalization in pleural mesothelioma |
| title_full_unstemmed | Co-targeting of VEGFR2 and PD-L1 promotes survival and vasculature normalization in pleural mesothelioma |
| title_short | Co-targeting of VEGFR2 and PD-L1 promotes survival and vasculature normalization in pleural mesothelioma |
| title_sort | co targeting of vegfr2 and pd l1 promotes survival and vasculature normalization in pleural mesothelioma |
| topic | Anti-angiogenesis cancer immunotherapy combination therapy immune checkpoint blockade pleural mesothelioma |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2512104 |
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