Lymphangiogenesis driven by VEGF-C reshapes tumor immune landscape and enables tumor eradication by viral immunotherapy in mouse melanoma models.

Authors

Ruben Fernandez-Rodriguez, Sara Cuadrado-Castano, Andrew Edwards, Anita Rogic, Yonina Bykov, Ignacio Mena, Noelia Dasilva-Freire, Camila Ceballos Paredes, Alice O Kamphorst, Rosa Karlic, Amir Horowitz, Adolfo García-Sastre, Mihaela Skobe

Published in

Cell reports. Volume 45. Issue 10. Pages 118130. Oct 15, 2026. Epub Oct 15, 2026.

Abstract

Vascular Endothelial Growth Factor C (VEGF-C), a key lymphangiogenic growth factor, has been implicated in improving responses to cancer immunotherapy. We investigated the impact of VEGF-C on the efficacy of oncolytic virotherapy with avian paramyxoviruses APMV-1 (NDV) and APMV-4. Treatment of B16F10 tumors lacking VEGF-C delays tumor growth, and complete responses (CRs) are rare. In contrast, virotherapy of VEGF-C-expressing tumors leads to CRs in most mice. Rechallenged mice remain tumor- and metastasis-free for over two years, indicating durable immunity. VEGF-C-induced lymphangiogenesis correlates with high CD8⁺ and CD4⁺ T cell densities near lymphatic vessels. Spectral flow cytometry shows changes in the composition and activation of CD8⁺ T cells, CD4⁺ T cells and NK cells associated with CRs, including enrichment of CD8⁺CD25⁺PD-1⁺ effector T cells. T cell composition changes in sentinel and contralateral lymph nodes, indicating a systemic response. These findings demonstrate that VEGF-C-driven remodeling of the tumor immune microenvironment enables durable CRs to APMV virotherapy.

PMID:
42886552
Bibliographic data and abstract were imported from PubMed on 17 Oct 2026.

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