Breaking News
March 19, 2019 - Scientists reverse alcohol-seeking behavior in rats with flip of a switch
March 19, 2019 - Researchers hope blood test that accurately diagnoses fibromyalgia could be available within five years
March 19, 2019 - New Planmeca ProScanner 2.0 offers fast and dependable intraoral imaging
March 19, 2019 - A new option for reducing LDL cholesterol in patients at high risk for heart attack, stroke
March 19, 2019 - Common medications to treat heartburn linked to increased risks for kidney failure
March 19, 2019 - Current HBV genome sequences help deduce ancient human population movements into Australia
March 19, 2019 - Pure omega-3 prescription drug significantly reduces the occurrence of ischemic events
March 19, 2019 - Researchers use big data to gain better understanding of hepatitis E virus
March 19, 2019 - Use of synthetic psychedelic linked to improvements in depression and anxiety
March 19, 2019 - Knee Pain Not Tied to Activity Levels in Knee Osteoarthritis
March 19, 2019 - Study shows benefits of delayed cord clamping in healthy babies
March 19, 2019 - Pharmacists can undertake overall clinical responsibility for patients, shows study
March 19, 2019 - A cell’s “self-destruct” function could yield new therapies
March 19, 2019 - Latest advances and perspectives of all AI types used in pharmaceutical R&D
March 19, 2019 - Prophylactic cranial irradiation used as standard approach for patients with NSCLC
March 19, 2019 - Sugar-sweetened beverages may be linked with increased risk of cardiovascular mortality
March 19, 2019 - AHA News: Black Woman in Their 50s Face Especially High Stroke Risk
March 19, 2019 - Secrets of early life revealed from less than half a teaspoon of blood
March 19, 2019 - Immune cells engineered to tattle on suspicious cells in the body
March 19, 2019 - Heart attack patients who are taken to heart care centres directly survive longer
March 19, 2019 - IVF babies have increased in birthweight over the past 25 years, study reveals
March 19, 2019 - Study highlights the need for psychiatric care to be integrated into cancer treatment
March 19, 2019 - Testosterone treatment lowers recurrence rates in low-risk prostate cancer patients
March 19, 2019 - Caterpillars could hold the secret to new treatment for Osteoarthritis
March 19, 2019 - Parkinson’s treatment delivers a power-up to brain cell ‘batteries’
March 19, 2019 - Stanford launches new Institute for Human-Centered Artificial Intelligence
March 19, 2019 - Wireless earphones may cause cancer
March 18, 2019 - ACC/AHA guideline for prevention of cardiovascular disease released
March 18, 2019 - UTA nursing professor receives $6.575 million to attack musculoskeletal diseases
March 18, 2019 - Gene medication shows promise to treat spinal cord injuries
March 18, 2019 - First Human Study of “Robotic” RaniPill™ Capsule to Replace Injections Announced by Rani Therapeutics
March 18, 2019 - Food Allergy Testing: MedlinePlus Lab Test Information
March 18, 2019 - Altered brain activity patterns of Parkinson’s captured in mice
March 18, 2019 - Apple Heart Study demonstrates ability of wearable technology to detect atrial fibrillation | News Center
March 18, 2019 - Cardiovascular benefits of diabetes drug extend across a wide spectrum of patients, shows study
March 18, 2019 - Novel cardiac pump shows superior outcomes in patients with advanced heart failure
March 18, 2019 - U.S. FDA Grants Priority Review for Fedratinib New Drug Application in Myelofibrosis
March 18, 2019 - Living like a caveman won’t make you thin—but it might make you healthy
March 18, 2019 - Modified immune cells issue alert when detecting cancer in mice | News Center
March 18, 2019 - Dementia caregivers design robots for alleviating stress and increasing joyful moments
March 18, 2019 - VR technology could help improve balance in humans
March 18, 2019 - Study demonstrates effective way to slow progression of cerebrovascular disease in older adults
March 18, 2019 - Premature babies also have protective anti-viral antibodies
March 18, 2019 - Painkillers taken by pregnant mothers unlikely to cause asthma in the child
March 18, 2019 - Fibromyalgia can be reliably detected in blood samples
March 18, 2019 - Marijuana use has dropped among most teens after legalization
March 18, 2019 - Legacy Pharmaceutical Packaging, LLC Issues Voluntary Nationwide Recall of Losartan Potassium Tablets, USP, 25mg, 50mg, And 100mg Due to The Detection of Trace Amounts Of N-Nitroso N-Methyl 4-Amino Butyric Acid (NMBA) Impurity Found in The Active Pharmaceutical Ingredient (API)
March 18, 2019 - Researchers identify early home and family factors that contribute to obesity
March 18, 2019 - Fate and festivity: Match Day 2019
March 18, 2019 - Study finds TAVR to be as good as open-heart surgery for patients at low surgical risk
March 18, 2019 - EU-funded project is developing new tools for diagnosing cancer
March 18, 2019 - Gluten, lactose, food dyes in pills could be causing side effects finds study
March 18, 2019 - Taking painkillers during pregnancy is not responsible for asthma risk in children, study shows
March 18, 2019 - Prediagnosis Psychiatric Care Linked to Worse Cancer Mortality
March 18, 2019 - Paris hospital halts stool study after donor deluge
March 18, 2019 - Partial oral antibiotic therapy shows efficacy and safety in patients with infectious endocarditis
March 18, 2019 - Olympus improves access to science education through BioBus collaboration
March 18, 2019 - Depression screening does not improve quality of life in heart attack patients
March 18, 2019 - Echocardiography may aid in patient selection for TMVR
March 18, 2019 - Are ‘Inactive’ Ingredients in Your Drugs Really So Harmless?
March 18, 2019 - Wearable technology can safely identify atrial fibrillation
March 18, 2019 - Scientists tackle rare retinal disease in unique research project
March 18, 2019 - Death By A Thousand Clicks
March 18, 2019 - Absorbable, antibiotic-eluting envelope can reduce rate of cardiac device infections
March 18, 2019 - Hormonal treatment associated with depression in men with prostate cancer
March 18, 2019 - Porvair Sciences launches reinforced 96-well deep round microplate
March 18, 2019 - Simplified catheter ablation could slash waiting lists for atrial fibrillation patients
March 18, 2019 - BFR therapy as part of rehabilitation following ACL surgery may slow bone loss
March 18, 2019 - A human model to test implants for cataract surgery
March 18, 2019 - New risk adjustment model could reduce financial penalty for safety net hospitals
March 18, 2019 - NHS cancer patients’ wait to start treatment worrying
March 18, 2019 - Inventiva Announces Results from Phase IIb Clinical Trial with Lanifibranor in Systemic Sclerosis
March 18, 2019 - Cologuard
March 18, 2019 - Researchers find evidence of prenatal environment tuning genomic imprinting
March 18, 2019 - Dolomite Bio launches novel Nadia product family for single-cell research
March 18, 2019 - Intellipharmaceutics Announces Resubmission of New Drug Application to the U.S. FDA for its Oxycodone ER
March 18, 2019 - Excessive gestational weight gain tied to maternal morbidity
March 18, 2019 - RCEM issues position statement on metrics to supplement four-hour standard target
March 17, 2019 - Noncontrast Brain MRI Effective for Monitoring Multiple Sclerosis
March 17, 2019 - Brain region plays key role in regulation of parenting behavior, study finds
Older melanoma patients fare better on immune checkpoint blockade therapy

Older melanoma patients fare better on immune checkpoint blockade therapy

image_pdfDownload PDFimage_print

Patient age correlates with response to immunotherapy in melanoma and depleting regulatory T cells in young patients may have a therapeutic potential to enhance response in younger patients, according to research from The Wistar Institute. Study results were published online in Clinical Cancer Research.

Immune checkpoint blockade therapy has been recently approved for treatment of melanoma based on its ability to produce durable disease control. Not all patients benefit from this therapeutic approach and some responders eventually develop resistance, highlighting the need for biomarkers that could help predict patient benefit and guide therapeutic choices.

“We have shown that the characteristics of the aged tumor microenvironment in older patients promote resistance to melanoma targeted therapies, highlighting the importance of considering patient age when predicting response to therapy,” said Ashani Weeraratna, Ph.D., Ira Brind Associate Professor and co-program leader of the Immunology, Microenvironment and Metastasis Program at Wistar and corresponding author of the paper.

Based on this consideration, Weeraratna and collaborators set to analyze the impact of age on response to immunotherapy. “We were initially surprised to find that older patients fare better on immune checkpoint blockade therapy,” she added.

The researchers analyzed a multi-national, multi-institutional cohort of almost 500 melanoma patients treated with pembrolizumab, an anti-programmed cell death receptor-1 (PD1) checkpoint therapy. They observed a significant difference in response to treatment by age, specifically that older patients had a decreased chance of disease progression after therapy, irrespective of gender and prior treatment with targeted therapies.

This observation was confirmed in mouse models of melanoma. In fact, genetically identical tumors responded more to anti-PD1 treatment when transplanted in old mice than in young mice, suggesting that the difference is ascribable to the environment in which the tumor develops.

The researchers analyzed the immune cell composition of the old and young tumor microenvironment both in patient-derived tissues and in mouse models and found a significant decrease in tumor infiltration of regulatory T cells (Treg) with age. These cells, characterized by expression of the FOXP3 marker, suppress the anti-tumor immune response and reduce response to anticancer immunotherapy. In parallel with a decrease in the percentage of Treg cells, older age correlated with increased presence of killer CD8 T cells, which are the primary effectors in the response to immune checkpoint blockade therapy.

Based on these observations, the researchers depleted Treg cells in the young mouse model by targeting them with an antibody against CD25, which is predominantly expressed at high levels on Treg cells. Combining anti-PD1 and anti-CD25 treatment was significantly more effective than anti-PD1 alone and they obtained response rates similar to those seen in aged mice, suggesting that overcoming the immune suppression observed in the young microenvironment helps to restore sensitivity to immunotherapy.

“Our study shows that age is an important factor to consider when administering immunotherapy to melanoma patients,” added Weeraratna. “A combination approach to deplete immune suppressive cells in combination with checkpoint blockade therapy might benefit younger patients, although further studies will be required to evaluate more broadly the potential immune toxicities of this approach.”

Source:

https://wistar.org/news/press-releases/older-melanoma-patients-have-better-response-immune-checkpoint-blockade-therapy

Tagged with:

About author

Related Articles