Characterisation of the tumour microenvironment and PD-L1 granularity reveals the prognostic value of cancer-associated myofibroblasts in non-invasive bladder cancer
High-risk non-muscle-invasive bladder cancer (NMIBC) presents high recurrence and progression rates. Despite the use of Bacillus Calmette-Guérin gold-standard immunotherapy and the recent irruption of anti-PD-1/PD-L1 drugs, we are missing a comprehensive understanding of the tumor microenvironment (...
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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.2024.2438291 |
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| author | Carmen G. Cañizo Félix Guerrero-Ramos Mercedes Perez Escavy Iris Lodewijk Cristian Suárez-Cabrera Lucía Morales Sandra P. Nunes Ester Munera-Maravilla Carolina Rubio Rebeca Sánchez Marta Rodriguez-Izquierdo Jaime Martínez de Villarreal Francisco X. Real Daniel Castellano Cristina Martín-Arriscado David Lora Pablos Alfredo Rodríguez Antolín Marta Dueñas Jesús M. Paramio Victor G. Martínez |
| author_facet | Carmen G. Cañizo Félix Guerrero-Ramos Mercedes Perez Escavy Iris Lodewijk Cristian Suárez-Cabrera Lucía Morales Sandra P. Nunes Ester Munera-Maravilla Carolina Rubio Rebeca Sánchez Marta Rodriguez-Izquierdo Jaime Martínez de Villarreal Francisco X. Real Daniel Castellano Cristina Martín-Arriscado David Lora Pablos Alfredo Rodríguez Antolín Marta Dueñas Jesús M. Paramio Victor G. Martínez |
| author_sort | Carmen G. Cañizo |
| collection | DOAJ |
| description | High-risk non-muscle-invasive bladder cancer (NMIBC) presents high recurrence and progression rates. Despite the use of Bacillus Calmette-Guérin gold-standard immunotherapy and the recent irruption of anti-PD-1/PD-L1 drugs, we are missing a comprehensive understanding of the tumor microenvironment (TME) that may help us find biomarkers associated to treatment outcome. Here, we prospectively analyzed TME composition and PD-L1 expression of tumor and non-tumoral tissue biopsies from 73 NMIBC patients and used scRNA-seq, transcriptomic cohorts and tissue micro-array to validate the prognostic value of cell types of interest. Compared to non-tumoral tissue, NMIBC presented microvascular alterations, increased cancer-associated fibroblast (CAF) and myofibroblast (myoCAF) presence, and varied immune cell distribution, such as increased macrophage infiltration. Heterogeneous PD-L1 expression was observed across subsets, with macrophages showing the highest expression levels, but cancer cells as the primary potential anti-PD-L1 binding targets. Unbiased analysis revealed that myoCAF and M2-like macrophages are specifically enriched in high-grade NMIBC tumors. The topological distribution of these two cell types changed as NMIBC progresses, as shown by immunofluorescence. Only myoCAFs were associated with higher rates of progression and recurrence in three independent cohorts (888 total patients), reaching prediction values comparable to transcriptomic classes, which we further validated using tissue micro-array. Our study provides a roadmap to establish the landscape of the NMIBC TME, highlighting myoCAFs as potential prognostic markers. |
| format | Article |
| id | doaj-art-3e9ed1121f8b4b04a35bdf2fcc03c8e2 |
| institution | DOAJ |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-3e9ed1121f8b4b04a35bdf2fcc03c8e22025-08-20T02:52:23ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2024.2438291Characterisation of the tumour microenvironment and PD-L1 granularity reveals the prognostic value of cancer-associated myofibroblasts in non-invasive bladder cancerCarmen G. Cañizo0Félix Guerrero-Ramos1Mercedes Perez Escavy2Iris Lodewijk3Cristian Suárez-Cabrera4Lucía Morales5Sandra P. Nunes6Ester Munera-Maravilla7Carolina Rubio8Rebeca Sánchez9Marta Rodriguez-Izquierdo10Jaime Martínez de Villarreal11Francisco X. Real12Daniel Castellano13Cristina Martín-Arriscado14David Lora Pablos15Alfredo Rodríguez Antolín16Marta Dueñas17Jesús M. Paramio18Victor G. Martínez19Urology Department, University Hospital ‘12 de Octubre’, Madrid, SpainUrology Department, University Hospital ‘12 de Octubre’, Madrid, SpainMolecular and Translational Oncology Division, Biomedical Innovation Unit, CIEMAT, Madrid, SpainMolecular and Translational Oncology Division, Biomedical Innovation Unit, CIEMAT, Madrid, SpainMolecular and Translational Oncology Division, Biomedical Innovation Unit, CIEMAT, Madrid, SpainMolecular and Translational Oncology Division, Biomedical Innovation Unit, CIEMAT, Madrid, SpainMolecular and Translational Oncology Division, Biomedical Innovation Unit, CIEMAT, Madrid, SpainMolecular and Translational Oncology Division, Biomedical Innovation Unit, CIEMAT, Madrid, SpainMolecular and Translational Oncology Division, Biomedical Innovation Unit, CIEMAT, Madrid, SpainCell Technology Division, Biomedical Innovation Unit, CIEMAT, Madrid, SpainUrology Department, University Hospital ‘12 de Octubre’, Madrid, SpainCentro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, SpainCentro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, SpainOncology Department, University Hospital ‘12 de Octubre’, Madrid, SpainScientific Support Unit, Research Institute I+12, University Hospital 12 de Octubre, Madrid, SpainScientific Support Unit, Research Institute I+12, University Hospital 12 de Octubre, Madrid, SpainUrology Department, University Hospital ‘12 de Octubre’, Madrid, SpainMolecular and Translational Oncology Division, Biomedical Innovation Unit, CIEMAT, Madrid, SpainMolecular and Translational Oncology Division, Biomedical Innovation Unit, CIEMAT, Madrid, SpainMolecular and Translational Oncology Division, Biomedical Innovation Unit, CIEMAT, Madrid, SpainHigh-risk non-muscle-invasive bladder cancer (NMIBC) presents high recurrence and progression rates. Despite the use of Bacillus Calmette-Guérin gold-standard immunotherapy and the recent irruption of anti-PD-1/PD-L1 drugs, we are missing a comprehensive understanding of the tumor microenvironment (TME) that may help us find biomarkers associated to treatment outcome. Here, we prospectively analyzed TME composition and PD-L1 expression of tumor and non-tumoral tissue biopsies from 73 NMIBC patients and used scRNA-seq, transcriptomic cohorts and tissue micro-array to validate the prognostic value of cell types of interest. Compared to non-tumoral tissue, NMIBC presented microvascular alterations, increased cancer-associated fibroblast (CAF) and myofibroblast (myoCAF) presence, and varied immune cell distribution, such as increased macrophage infiltration. Heterogeneous PD-L1 expression was observed across subsets, with macrophages showing the highest expression levels, but cancer cells as the primary potential anti-PD-L1 binding targets. Unbiased analysis revealed that myoCAF and M2-like macrophages are specifically enriched in high-grade NMIBC tumors. The topological distribution of these two cell types changed as NMIBC progresses, as shown by immunofluorescence. Only myoCAFs were associated with higher rates of progression and recurrence in three independent cohorts (888 total patients), reaching prediction values comparable to transcriptomic classes, which we further validated using tissue micro-array. Our study provides a roadmap to establish the landscape of the NMIBC TME, highlighting myoCAFs as potential prognostic markers.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2438291Bladder cancercancer-associated fibroblastsMyofibroblastsPD-L1tumor microenvironment |
| spellingShingle | Carmen G. Cañizo Félix Guerrero-Ramos Mercedes Perez Escavy Iris Lodewijk Cristian Suárez-Cabrera Lucía Morales Sandra P. Nunes Ester Munera-Maravilla Carolina Rubio Rebeca Sánchez Marta Rodriguez-Izquierdo Jaime Martínez de Villarreal Francisco X. Real Daniel Castellano Cristina Martín-Arriscado David Lora Pablos Alfredo Rodríguez Antolín Marta Dueñas Jesús M. Paramio Victor G. Martínez Characterisation of the tumour microenvironment and PD-L1 granularity reveals the prognostic value of cancer-associated myofibroblasts in non-invasive bladder cancer OncoImmunology Bladder cancer cancer-associated fibroblasts Myofibroblasts PD-L1 tumor microenvironment |
| title | Characterisation of the tumour microenvironment and PD-L1 granularity reveals the prognostic value of cancer-associated myofibroblasts in non-invasive bladder cancer |
| title_full | Characterisation of the tumour microenvironment and PD-L1 granularity reveals the prognostic value of cancer-associated myofibroblasts in non-invasive bladder cancer |
| title_fullStr | Characterisation of the tumour microenvironment and PD-L1 granularity reveals the prognostic value of cancer-associated myofibroblasts in non-invasive bladder cancer |
| title_full_unstemmed | Characterisation of the tumour microenvironment and PD-L1 granularity reveals the prognostic value of cancer-associated myofibroblasts in non-invasive bladder cancer |
| title_short | Characterisation of the tumour microenvironment and PD-L1 granularity reveals the prognostic value of cancer-associated myofibroblasts in non-invasive bladder cancer |
| title_sort | characterisation of the tumour microenvironment and pd l1 granularity reveals the prognostic value of cancer associated myofibroblasts in non invasive bladder cancer |
| topic | Bladder cancer cancer-associated fibroblasts Myofibroblasts PD-L1 tumor microenvironment |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2438291 |
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