HOXD13 Protein Fuels Melanoma Growth, Blocks Immune Attack
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- HOXD13 emerged as a central regulator of melanoma in a study published in Cancer Discovery, activating VEGF, SEMA3A, and CD73 pathways to boost tumor blood supply while suppressing cytotoxic T cell activity.
- NYU Langone Health researchers, led by Pietro Berico, PhD, and senior investigator Eva Hernando-Monge, PhD, found that melanoma patients with high HOXD13 levels had fewer cytotoxic T cells circulating and reduced T cell infiltration into tumors.
- HOXD13 raises adenosine levels via CD73, creating a protective barrier that blocks T cells from entering cancerous tissue; disabling HOXD13 shrank tumors and reopened tumor access to immune cells in mouse and cell-line experiments.
- The study analyzed tumor samples from more than 200 melanoma patients across the U.S., Brazil, and Mexico, with additional collaborators from the National Autonomous University of Mexico and Brazil's National Cancer Institute.
- Hernando-Monge said the findings support combining VEGF-receptor and adenosine-receptor inhibitors—already in clinical trials—for patients with high HOXD13 levels, and the team plans to test this approach in glioblastomas, sarcomas, and osteosarcomas where HOXD13 is also elevated.
Why it matters: Melanoma patients with high HOXD13 may respond poorly to existing immunotherapy because the protein builds both a blood-supply lifeline and an adenosine-based immune shield around tumors. Existing VEGF and adenosine-receptor inhibitors—already in clinical trials—could be repurposed as a targeted combination, with a biomarker (HOXD13) to select patients most likely to benefit.
