Researchers at NYU Langone Health have identified the protein HOXD13 as a key driver of melanoma tumors, promoting blood vessel growth and blocking immune attacks. Disabling HOXD13 in experiments shrank tumors and allowed T cells to infiltrate more effectively. The findings suggest new combination treatments targeting angiogenesis and immune pathways.
A team led by Pietro Berico, PhD, and Eva Hernando-Monge, PhD, from NYU Grossman School of Medicine and Perlmutter Cancer Center found that HOXD13 activates pathways for angiogenesis, including vascular endothelial growth factor (VEGF), semaphorin-3A (SEMA3A), and CD73. This boosts blood supply to tumors while elevating adenosine levels, which hinders cytotoxic T cells from entering and attacking cancer cells. Patients with high HOXD13 showed fewer T cells in their blood and reduced tumor infiltration by these immune fighters. Experiments in mice and human melanoma cell lines confirmed that reducing HOXD13 activity led to smaller tumors and restored T cell access. The study analyzed tumor samples from over 200 melanoma patients across the U.S., Brazil, and Mexico, published in Cancer Discovery. Collaborators included researchers from the National Autonomous University of Mexico and the Brazilian National Cancer Institute. Berico stated, 'Our study provides new evidence that transcription factor HOXD13 is a potent driver of melanoma growth and that it suppresses the T cell activity needed to fight the disease.' Hernando-Monge added, 'This data supports the combined targeting of angiogenesis and adenosine-receptor pathways as a promising new treatment approach for HOXD13-driven melanoma.' The team plans to test VEGF and adenosine-receptor inhibitors, potentially combined with immunotherapy, in patients with elevated HOXD13. Similar pathways may apply to other cancers like glioblastomas and sarcomas.
