During tumorigenesis, the hypoxic tumour environment promotes the formation of new blood vessels that show many abnormalities compared with healthy vasculature. Leukocyte adhesion to endothelial cells lining the tumour-associated vasculature is impaired and, consequently, effector immune cells cannot gain access to the tumour. In this study, the authors treated tumour-bearing mice with a tumour necrosis factor (TNF)–peptide fusion protein that targets TNF to the tumour-associated vasculature. They found that this therapy promoted the upregulation of adhesion molecules on endothelial cells and increased the infiltration of CD8+ T cells into tumours. In mice with ovalbumin-expressing tumours, delivery of the fusion protein markedly increased the antitumour responses of adoptively transferred ovalbumin-specific CD8+ T cells. The authors suggest that a similar approach could be used to improve the efficacy of adoptive T cell transfer-based therapies for cancer.
ORIGINAL RESEARCH PAPER
Calcinotto, A. et al. Targeting TNF-α to neoangiogenic vessels enhances lymphocyte infiltration in tumors and increases the therapeutic potential of immunotherapy. J. Immunol. 188, 2687–2694 (2012)Article
Rights and permissions
About this article
Cite this article
Bordon, Y. Hope in a sticky situation. Nat Rev Immunol 12, 231 (2012). https://doi.org/10.1038/nri3205
Published:
Issue Date:
DOI: https://doi.org/10.1038/nri3205