Breaking News
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
March 17, 2019 - Natural speed limit on DNA replication sets pace for life’s first steps
March 17, 2019 - New research reveals overlooked impact of herbicide glyphosate on the environment
March 17, 2019 - Molecular patterns could help predict relapse risk in breast cancer patients
March 17, 2019 - Study confirms sensitivity of microbiological cultures for detecting cholera
March 17, 2019 - Scientists Spot Clues to Predicting Breast Cancer’s Return
March 17, 2019 - Scientists identify gene that keeps PTSD-like behavior at bay in female mice
March 17, 2019 - New method would allow doctors to detect earliest stages of cancers in the lymph nodes
March 17, 2019 - Cholesterol protein discovery raises hope for smarter drugs
March 17, 2019 - New insect medium delivers high viable cell density growth and protein yield
March 17, 2019 - Opioid crisis brings concerns about heart dangers
March 17, 2019 - Resistance Training May Prevent Type 2 Diabetes Progression
March 17, 2019 - Bioluminescence sensors make new approaches to drug discovery possible
March 17, 2019 - New FDA Rules Aim to Keep Kids From Flavored E-Cigarettes
March 17, 2019 - Vitamin B3 analogue boosts production of blood cells
March 17, 2019 - Government cuts to stop smoking services have detrimental impact on public health
March 17, 2019 - Common tool to assess potential adoptive parents lags behind societal changes
March 17, 2019 - Patients’ own cells could be the key to treating Crohn’s disease
March 17, 2019 - Diagnostic delays common in inflammatory bowel disease
March 17, 2019 - Study uncovers dramatic differences in the brains of Hispanics with dementia
Study finds higher response to anti-PD1 immunotherapy in older melanoma patients

Study finds higher response to anti-PD1 immunotherapy in older melanoma patients

image_pdfDownload PDFimage_print

Bottom Line: With each decade of life, the likelihood of progression of melanoma after treatment with anti-PD1 immunotherapy decreased by 13 percent.

Journal in Which the Study was Published: Clinical Cancer Research, a journal of the American Association for Cancer Research.

Author: Ashani T. Weeraratna, PhD, the Ira Brind professor and co-program leader of the Immunology, Microenvironment and Metastasis Program at The Wistar Institute; and a member of Wistar’s Melanoma Research Center in Philadelphia

Background: “We wanted to study how the aging microenvironment affects response to immunotherapy, and much to our surprise, the effect was exactly the opposite of what we learned with targeted therapy,” said Weeraratna. Prior research by Weeraratna and colleagues had shown that the tumor microenvironment in older patients promoted melanoma metastasis and resistance to targeted therapy with a BRAF inhibitor.

How the Study Was Conducted and Results: In this multinational study, the researchers analyzed data from 538 patients with melanoma treated with the anti-PD1 therapy pembrolizumab (Keytruda) at eight different institutes worldwide. Of the patients, 238 were younger than 62 years. They found that 50 percent of patients younger than 62 years, compared with only 37 percent of patients 62 years or older, had poor response to the treatment. This finding was independent of gender or prior treatment with MAPK inhibitor (MAPKi) therapies.

“Interestingly, younger patients who had prior MAPKi therapy had a much lower rate of complete response to anti-PD1 than older patients who had prior MAPKi therapy (4 percent versus 15 percent),” Weeraratna said.

Weeraratna and colleagues conducted further experiments using mice bearing melanoma to understand the relationship between the aging microenvironment and response to anti-PD1 immunotherapy. The results from the studies with mice were in agreement with those from human patients: Young mice were more resistant to anti-PD1 therapies than aged mice. The results were also independent of tumor mutational burden, because both young and aged mice were implanted with genetically identical tumors but had different outcomes.

Further research revealed differences in the immune microenvironment of the two groups of mice. A subpopulation of T cells that are known to be immunosupressive, FOXP3-positive Tregs, were fewer in older mice compared with younger mice.

The team analyzed primary and metastatic melanoma samples from another cohort of 268 patients for the presence of the protein FOXP3 in T cells and found that the FOXP3-positivity of intratumoral T cells decreased in patients over 50 years of age. The researchers also observed age-related differences in the T-cell subpopulations within the tumors of these patients.

Her team found that in young mice, combining anti-PD1 with an anti-CD25 antibody therapy, which depletes Tregs, yielded response rates comparable to those seen in older mice.

Author’s Comments: “Our current study showed that for each decade of life, patients with melanoma had a 13 percent lower chance of having a negative outcome following anti-PD1 immunotherapy,” Weeraratna noted.

“Our results suggest that preconditioning the tumor microenvironment in younger patients by depleting Tregs could make them respond to anti-PD1 immunotherapies better,” she said. “Our studies suggest that in designing therapies for melanoma, age should be considered as a factor in both preclinical and clinical models.”

“Age has a huge impact on patients’ response to therapy and tumor progression,” Weeraratna noted. “Researchers conducting preclinical studies should ensure that the age of the mice reflects the age of the patients the treatments are intended for, as these studies form the basis for drug development and human clinical trials.”

Tagged with:

About author

Related Articles