A protein called HOHOX‑D13 (short: HOXD13) can turn on many genes. New research shows it helps skin cancer (melanoma) grow and hide from the body's defenses.
HOXD13 Feeds the Tumor
Scientists at NYU Langone found that HOXD13 makes blood vessels grow into the tumor. More vessels bring oxygen and food, so the tumor gets bigger.
The protein works through several pathways, including VEGF, SEMA3A, and CD73. When researchers lowered HOXD13 in lab tests, tumors shrank.
HOXD13 Stops the Immune System
Patients with high HOXD13 had fewer killer T‑cells in their blood. Those T‑cells also had a hard time getting into the tumor.
HOXD13 raises CD73, which makes more adenosine. Adenosine acts like a shield, slowing T‑cells and keeping them out of the tumor.
What This Means for Treatment
Blocking the blood‑vessel signals (VEGF) and the adenosine shield at the same time could be a strong new therapy for tumors with lots of HOXD13.
Clinical trials are already testing drugs that block VEGF or adenosine receptors, sometimes together with immunotherapy. If those trials succeed, doctors may add both blockers for patients with high HOXD13.
Beyond Melanoma
HOXD13 is also high in some brain tumors, sarcomas, and bone cancers. Researchers want to see if the same drug combos work there too.
How the Study Was Done
The team examined tumor samples from over 200 melanoma patients in the United States, Brazil, and Mexico. They saw that HOXD13 was linked to more blood‑vessel growth and fewer immune cells.
Experiments in mice and human melanoma cells confirmed these findings. Stopping HOXD13, VEGF, or adenosine made tumors shrink and let more T‑cells enter.
Funding
The work was paid for by the National Institutes of Health, the Melanoma Research Foundation, the Melanoma Research Alliance, the UK Medical Research Council, Brazil’s CNPQ, and the Wellcome Trust.