Angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombus
Abstract Venous tumour thrombus (VTT), where the primary tumour invades the renal vein and inferior vena cava, affects 10–15% of renal cell carcinoma (RCC) patients. Curative surgery for VTT is high-risk, but neoadjuvant therapy may improve outcomes. The NAXIVA trial demonstrated a 35% VTT response...
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Nature Portfolio
2025-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58436-8 |
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| author | Rebecca Wray Hania Paverd Ines Machado Johanna Barbieri Farhana Easita Abigail R. Edwards Ferdia A. Gallagher Iosif A. Mendichovszky Thomas J. Mitchell Maike de la Roche Jacqueline D. Shields Stephan Ursprung Lauren Wallis Anne Y. Warren Sarah J. Welsh Mireia Crispin-Ortuzar Grant D. Stewart James O. Jones On behalf of the NAXIVA Study Group |
| author_facet | Rebecca Wray Hania Paverd Ines Machado Johanna Barbieri Farhana Easita Abigail R. Edwards Ferdia A. Gallagher Iosif A. Mendichovszky Thomas J. Mitchell Maike de la Roche Jacqueline D. Shields Stephan Ursprung Lauren Wallis Anne Y. Warren Sarah J. Welsh Mireia Crispin-Ortuzar Grant D. Stewart James O. Jones On behalf of the NAXIVA Study Group |
| author_sort | Rebecca Wray |
| collection | DOAJ |
| description | Abstract Venous tumour thrombus (VTT), where the primary tumour invades the renal vein and inferior vena cava, affects 10–15% of renal cell carcinoma (RCC) patients. Curative surgery for VTT is high-risk, but neoadjuvant therapy may improve outcomes. The NAXIVA trial demonstrated a 35% VTT response rate after 8 weeks of neoadjuvant axitinib, a VEGFR-directed therapy. However, understanding non-response is critical for better treatment. Here we show that response to axitinib in this setting is characterised by a distinct and predictable set of features. We conduct a multiparametric investigation of samples collected during NAXIVA using digital pathology, flow cytometry, plasma cytokine profiling and RNA sequencing. Responders have higher baseline microvessel density and increased induction of VEGF-A and PlGF during treatment. A multi-modal machine learning model integrating features predict response with an AUC of 0.868, improving to 0.945 when using features from week 3. Key predictive features include plasma CCL17 and IL-12. These findings may guide future treatment strategies for VTT, improving the clinical management of this challenging scenario. |
| format | Article |
| id | doaj-art-e0db2dfec9d340c49f4b478d9f2fd2b0 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e0db2dfec9d340c49f4b478d9f2fd2b02025-08-20T03:52:24ZengNature PortfolioNature Communications2041-17232025-04-0116111410.1038/s41467-025-58436-8Angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombusRebecca Wray0Hania Paverd1Ines Machado2Johanna Barbieri3Farhana Easita4Abigail R. Edwards5Ferdia A. Gallagher6Iosif A. Mendichovszky7Thomas J. Mitchell8Maike de la Roche9Jacqueline D. Shields10Stephan Ursprung11Lauren Wallis12Anne Y. Warren13Sarah J. Welsh14Mireia Crispin-Ortuzar15Grant D. Stewart16James O. Jones17On behalf of the NAXIVA Study GroupEarly Cancer Institute, University of CambridgeEarly Cancer Institute, University of CambridgeEarly Cancer Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Centre, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCambridge University Hospitals NHS Foundation TrustCambridge University Hospitals NHS Foundation TrustEarly Cancer Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeTranslational Medical Sciences, School of Medicine, University of Nottingham Biodiscovery InstituteCambridge University Hospitals NHS Foundation TrustWarwick Medical School, University of WarwickCambridge University Hospitals NHS Foundation TrustRoyal Devon University Healthcare NHS Foundation TrustEarly Cancer Institute, University of CambridgeCancer Research UK Cambridge Centre, University of CambridgeDepartment of Oncology, University of CambridgeAbstract Venous tumour thrombus (VTT), where the primary tumour invades the renal vein and inferior vena cava, affects 10–15% of renal cell carcinoma (RCC) patients. Curative surgery for VTT is high-risk, but neoadjuvant therapy may improve outcomes. The NAXIVA trial demonstrated a 35% VTT response rate after 8 weeks of neoadjuvant axitinib, a VEGFR-directed therapy. However, understanding non-response is critical for better treatment. Here we show that response to axitinib in this setting is characterised by a distinct and predictable set of features. We conduct a multiparametric investigation of samples collected during NAXIVA using digital pathology, flow cytometry, plasma cytokine profiling and RNA sequencing. Responders have higher baseline microvessel density and increased induction of VEGF-A and PlGF during treatment. A multi-modal machine learning model integrating features predict response with an AUC of 0.868, improving to 0.945 when using features from week 3. Key predictive features include plasma CCL17 and IL-12. These findings may guide future treatment strategies for VTT, improving the clinical management of this challenging scenario.https://doi.org/10.1038/s41467-025-58436-8 |
| spellingShingle | Rebecca Wray Hania Paverd Ines Machado Johanna Barbieri Farhana Easita Abigail R. Edwards Ferdia A. Gallagher Iosif A. Mendichovszky Thomas J. Mitchell Maike de la Roche Jacqueline D. Shields Stephan Ursprung Lauren Wallis Anne Y. Warren Sarah J. Welsh Mireia Crispin-Ortuzar Grant D. Stewart James O. Jones On behalf of the NAXIVA Study Group Angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombus Nature Communications |
| title | Angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombus |
| title_full | Angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombus |
| title_fullStr | Angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombus |
| title_full_unstemmed | Angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombus |
| title_short | Angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombus |
| title_sort | angiogenic and immune predictors of neoadjuvant axitinib response in renal cell carcinoma with venous tumour thrombus |
| url | https://doi.org/10.1038/s41467-025-58436-8 |
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