Harnessing the gene behind hair loss could help improve cancer immunotherapy.
A study by Columbia University Irving Medical Center researchers confirmed the possibility. "While immunotherapies have shown great promise in cancer, most patients do not benefit from these treatments because their tumours are able to evade the immune system," said a lead researcher, Angela M. Christiano.
"But one way around this obstacle is to harness genes that cause the recruitment of T cells in autoimmune disease and use them to attract T cells to kill tumours. In this study, we showed that a gene that recruits T cells in alopecia areata- a condition in which immune cells attack and destroy hair cells--is turned off in various types of cancer, protecting them from the immune system. But if we turn that gene back on, we can make those cancers vulnerable to the immune response," he added.
The study began with the recognition that auto-immune diseases and cancer represent opposite ends of the immune signalling spectrum. When the immune system is overactive, a patient may be at risk for auto-immune disease; when it's underactive, cancer can evade the immune system and progress. "We should be able to identify genetic signals that are hyperactive in autoimmune disease, and then harness those signals in tumours that have developed a way to avoid the immune response," said another researcher, James Chen.
In a previous study, the researchers identified a genetic signal, which is a gene called named IKZF1- in alopecia areata. In this condition, an overactive IKZF1 gene leads to overproduction of immune cells, killing the hair follicles.
The key immune cells in alopecia areata are the same cells that many cancers can evade, but the killer T cells are crucial for the success of cancer immunotherapies. In this study, the researchers investigated whether they could activate IKZF1 in tumour cells in order to attract T cells to tumours, mobilizing them to attack cancer.
"We were particularly struck that IKZF1-expressing tumours responded significantly better to anti-PD-1 and anti-CTLA-4 treatment. Tumour growth was almost completely suppressed," said another researcher, Charles G. Drake.
The team analyzed data from a previous study of melanoma patients with disabled IKZF1. It was found that patients with disabled IKZF1 had higher recurrence rates and worse survival compared to other melanoma patients."Clinically, this is an especially exciting finding, since prostate cancer is generally very poorly infiltrated by immune cells. Turning these 'cold' tumours' hot' could be a key to therapeutic success," said Drake.
The study appears in the Cell Systems journal.