Breaking News
December 10, 2018 - People covered by Michigan’s expanded Medicaid program report improvements in health, finds study
December 10, 2018 - Hazelnuts improve micronutrient levels in older adults
December 9, 2018 - History of Partner Violence Tied to Menopause Symptoms
December 9, 2018 - Clean Up Safely After a Disaster|Natural Disasters and Severe Weather
December 9, 2018 - Drug wholesalers drove fentanyl’s deadly rise, report concludes
December 9, 2018 - Deprescribing could help manage polypharmacy in older adults
December 9, 2018 - Retraction of article “Joy of cooking too much” from journal
December 9, 2018 - FDA Warns of Rare Stroke Risk With MS Drug Lemtrada (Alemtuzumab)
December 9, 2018 - Feds say heroin, fentanyl remain biggest drug threat to US
December 9, 2018 - Eliminating microglia can reverse some aspects of stress sensitization, study shows
December 9, 2018 - New genetic insight could help treat rare debilitating heart and lung condition
December 9, 2018 - MiRagen Therapeutics Announces Final Safety, Biodistribution and Clinical Efficacy Data From Phase 1 Cobomarsen Clinical Trial in Patients With Mycosis Fungoides
December 9, 2018 - Work with your doctor to weigh pros, cons of treatment options for hyperthyroidism
December 9, 2018 - CWRU researcher secures $14.6 million funding for genetic study into Alzheimer’s disease
December 9, 2018 - High intensity statin treatment and adherence could save more lives
December 9, 2018 - Surgery patients use only 1/4 of prescribed opioids, and prescription size matters
December 9, 2018 - AXT offers Phi Optics upgrade to QPI systems for inverted light microscopes
December 9, 2018 - New booklet could help improve conditions of young pupils with albinism
December 9, 2018 - Few Physicians Work in Practices That Use Telemedicine
December 9, 2018 - Older Adults and Oral Health
December 9, 2018 - Health utility values improve after septorhinoplasty
December 9, 2018 - New EU-funded project provides insight into how the brain develops
December 9, 2018 - Expanded use of tele-emergency services can help strengthen rural hospitals
December 9, 2018 - Infections in the Young May Be Tied to Risk for Mental Illness: Study
December 9, 2018 - Profile: Native Hawaiians and Pacific Islanders
December 9, 2018 - Snoring poses greater cardiac risk to women
December 9, 2018 - Researcher takes further steps in understanding how and why cute aggression occurs
December 9, 2018 - Researchers create new light-activated tools for controlling neurons
December 9, 2018 - Spinal cord injury disrupts the body’s internal clock, study shows
December 9, 2018 - Babies recognize nested structures similar to our grammar
December 9, 2018 - UT Austin researcher receives $2.5 million CZI grant for neurodegenerative disease research
December 9, 2018 - Sleep problems found to be prevalent and increasing among college students
December 9, 2018 - Study reveals why some children are susceptible to the effects of maltreatment
December 9, 2018 - Study investigates influence of different opioids on driving performance
December 9, 2018 - Jazz Pharmaceuticals Announces First Patient Enrolled in Phase 3 Clinical Trial Evaluating JZP-258 for the Treatment of Idiopathic Hypersomnia
December 9, 2018 - Eliminating microglia prevents heightened immune sensitivity after stress
December 9, 2018 - Boys with social difficulties are at greatest risk of early substance use
December 9, 2018 - ‘Wrong’ connective tissue cells linked to worse prognosis in breast cancer patients
December 8, 2018 - Chronic, refractory schizophrenia patients benefit from targeted cognitive training
December 8, 2018 - Advertising in kids’ apps more prevalent than parents may realize
December 8, 2018 - New way to trace the transmission histories of rare genetic diseases
December 8, 2018 - ASH: A+CHP Bests CHOP for Peripheral T-Cell Lymphoma
December 8, 2018 - Results of pediatric genomic epilepsy tests often reclassified
December 8, 2018 - New way of controlling HIV latency to completely eradicate the virus
December 8, 2018 - Phasefocus to showcase the Livecyte 2 at ASCB
December 8, 2018 - KHN’s ‘What the Health?’ Is health spending the next big political issue?
December 8, 2018 - Mussels take in microplastic pollution fibers and flush most of them out again
December 8, 2018 - AHA: How to Stop Smoking … for Good
December 8, 2018 - Scientists overturn odds to make Parkinson’s discovery
December 8, 2018 - Health benefits of producing marula vinegar
December 8, 2018 - Failure of critical cellular energy sensor responsible for CKD progression, study finds
December 8, 2018 - Ethnicity can be reliable indicator of gut microbiota diversity
December 8, 2018 - Safe Sleep for Baby | NIH News in Health
December 8, 2018 - Study looks at ways technology can support nutritional needs of Parkinson’s patients
December 8, 2018 - Infant milk allergy is being overdiagnosed say experts
December 8, 2018 - Graphene may one day be used to test for ALS
December 8, 2018 - Houston Methodist launches real-time website to track flu cases
December 8, 2018 - RedHill Announces Positive Top-Line Results from Confirmatory Phase 3 Study with Talicia for H. pylori Infection
December 8, 2018 - A way to measure obesity and health beyond BMI
December 8, 2018 - New diagnostic tools may help identify breast cancer patients who could benefit from targeted therapies
December 8, 2018 - Duke-NUS researchers highlight possible role of bioaerosol sampling in pandemic surveillance
December 8, 2018 - Study quantifies links between alcohol, drug use and violent deaths
December 8, 2018 - Mothers’ stress levels at conception linked to child’s response to life challenges at age 11
December 8, 2018 - MIT researchers develop antimicrobial peptides from South American wasp’s venom
December 8, 2018 - Obesity prevention among low-income, diverse preschool-aged children and parents
December 8, 2018 - Mount Sinai researcher awarded $2.5 million to advance understanding of neurodegenerative diseases
December 8, 2018 - CZI announces funding for open-source software efforts to improve image analysis in biomedicine
December 8, 2018 - New book encompasses the vast history of reproduction
December 8, 2018 - Low-income women in Texas are not receiving contraception after childbirth, study shows
December 8, 2018 - Study expands knowledge about sexuality and gender gaps in political attitudes
December 8, 2018 - Drug reduces hot flash frequency, improves quality of life in breast cancer survivors
December 8, 2018 - Imaging, Biopsy Often Still Needed After Mastectomy
December 8, 2018 - Physical Activity Guidelines for Americans: 2nd edition
December 8, 2018 - Machine learning can improve chemical toxicity prediction
December 8, 2018 - Researchers explore why and how Mediterranean diet may mitigate cardiovascular risk
December 8, 2018 - Multigene test is a helpful decision making tool in breast cancer treatment, study shows
December 8, 2018 - New EZ-2 centrifugal evaporator to safely remove solvents from cytotoxic drug preparations
December 8, 2018 - UMGCCC uses Gammapod radiotherapy to treat breast cancer patients
December 8, 2018 - Men with inflammatory bowel disease have higher prostate cancer risk
December 8, 2018 - Newly developed molecules may provide more reliable relief for people with autoimmune diseases
Gene linked to hair loss could be exploited to improve cancer immunotherapy

Gene linked to hair loss could be exploited to improve cancer immunotherapy

image_pdfDownload PDFimage_print

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.

The paper was published on line last month in the journal Cell Systems.

“While immunotherapies have shown great promise in cancer, most patients do not benefit from these treatments because their tumors 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 tumors. 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.”

The study began with the recognition that autoimmune diseases and cancer represent opposite ends of the immune signaling 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 tumors 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 such a genetic signal–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. These so-called killer T cells are crucial for the success of cancer immunotherapies,” said Christiano.

In this study, the researchers investigated whether they could activate IKZF1 in tumor cells in order to attract T cells to tumors, 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 tumor 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 predictions were first tested in a mouse model of melanoma in which the tumors were genetically modified to express IKZF1. The mice were found to have increased levels of infiltrating immune cells in their tumors, compared to control mice with conventional melanoma, a sign that the tumors had lost as least some ability to evade the immune response.

“We were particularly struck that IKZF1-expressing tumors responded significantly better to anti-PD-1 and anti-CTLA-4 treatment. Tumor growth was almost completely suppressed,” said study co-author Charles G. Drake, MD, PhD, professor of medicine and director of genitourinary oncology at Columbia University Vagelos College of Physicians and Surgeons, co-director of the immunotherapy program, and associate director for clinical research of the Herbert Irving Comprehensive Cancer Center at CUIMC.

The team then analyzed data from a previous study of melanoma patients with disabled IKZF1. Patients with disabled IKZF1 had higher recurrence rates and worse survival compared to other melanoma patients.

The team is currently searching for additional candidate genes that can similarly be used to enhance the response to immunotherapy in melanoma.

The algorithm also predicted that prostate cancer could be made more responsive to immunotherapy. In lab experiments, the team found that restoring IKZF1 activity in prostate tumor cells made them susceptible to immunotherapies. “Clinically, this is an especially exciting finding, since prostate cancer is generally very poorly infiltrated by immune cells. Turning these ‘cold’ tumors ‘hot’ could be a key to therapeutic success,” said Drake.

In addition, the algorithm correctly predicted that colorectal and kidney tumors would not respond to immunotherapy if IKZF1 expression was increased, since the gene was found to be inactive in these tumors.

Therapies based on these findings would be years away, in large part because different approaches would be needed to activate IKZF1 in humans. However, the approach could be used soon to predict whether patients are likely to respond to immunotherapy and to assess their prognosis.

Source:

Harnessing Hair Loss Gene Could Improve Cancer Immunotherapy

Tagged with:

About author

Related Articles