Hope for Cancer Patients Found in Hair Loss Gene
A gene that’s associated with an autoimmune form of hair loss could be exploited to improve cancer immunotherapy, suggests a new mouse study by Columbia University Irving Medical Center (CUIMC) researchers.
“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 study leader Angela M. Christiano, PhD, the Richard and Mildred Rhodebeck Professor of Dermatology and Genetics and Development at Columbia University Vagelos College of Physicians and Surgeons. “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.
It was shown 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. However, if the gene was then turned back “on”, the cancers cells were then vulnerable to the immune response.
The study, published in Cell Systems, began with the recognition that autoimmune diseases and cancer represent opposite ends of the immune signalling spectrum. When the immune system is overactive, a patient may be at risk for autoimmune 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 lead author James Chen, PhD, a precision medicine fellow at CUIMC.
In a previous study, the research team identified a gene called named IKZF1 to be associated with onset of 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. These so-called killer T cells are crucial for the success of cancer immunotherapies,” said Christiano.
The researchers investigated whether they could activate IKZF1 in tumour cells in order to attract T cells to tumours, mobilizing them to attack the cancer.
Using an algorithm designed by Chen, the researchers screened genomic and bioinformatic data on thousands of cancer patients in the Cancer Genome Atlas, searching for tumour types that had IKZF1 in their regulatory networks. The algorithm predicted several types of cancer, including melanoma, that would be amenable to targeted immunotherapy, and two types that would not.
The theory was tested in mice. It was found to have increased levels of infiltrating immune cells in their tumours, compared to control mice with conventional melanoma, a sign that the tumours had lost as least some ability to evade the immune response.