Through a new study, researchers at Children's Hospital Boston and Brigham and Women's Hospital (BWH) have been able to shed light on how melanomas shield themselves from immune attack.
Although the immune system initially responds to melanoma and mounts anti-tumour attacks, these assaults are generally ineffective, allowing more advanced melanomas to spread beyond the primary site.
AdvertisementPrevious study by the same team, led by Markus Frank, MD, of the Transplantation Research Centre of Children's and BWH, and George Murphy, MD, chief of Dermatopathology at BWH revealed that the reason for melanoma virulence is a small group of tumour stem cells that are able to grow despite chemotherapy drugs, allowing the tumour to re-grow and progress.
They also showed that targeting these cells (identifiable by a molecule on their surface known as ABCB5) could successfully inhibit tumour growth in mice.
The new study has shown that these ABCB5-positive cells also produce molecules that inhibit the body's natural immune attack, known as PD-1 and B7.2.
These molecules work by triggering white blood cells known as regulatory T cells (T-regs), to dampen the normal anti-melanoma response.
The T-regs are thus tricked into protecting the deadly melanoma stem cells from the body's own defenses.
The study adds to a growing body of evidence that melanoma stem cells have developed a repertoire of complementary strategies to outsmart host defenses, camouflaging them from the very immune cells and therapeutic agents that seek to destroy them. It also suggests new strategies for attacking the deadly skin cancer.
"Melanoma stem cell targeting holds promise for an absolute cure, because you're hitting the cells that really matter - the cells that drive tumour progression," said Murphy.
"By understanding the precise molecular pathways whereby melanoma stem cells cajole the immune system into a permissive role, scientists are now closer to identifying ways of blocking or inhibiting such tactics," he added.
The study appears in journal Cancer Research.