Breaking News
September 25, 2018 - Study provides evidence of beta lactamase producing, antimicrobial resistant E. coli in U.S. retail meat
September 25, 2018 - UCI study finds new cause of cerebral microbleeds
September 25, 2018 - Researchers propose mechanism by which ASTN2 protein defects lead to brain disorders
September 25, 2018 - Chinese and German researchers to cooperate more closely in future for better food
September 25, 2018 - Recent study helps predict probability of pregnant mothers to have child with autism
September 25, 2018 - New online, sound matching tool offers tinnitus sufferers potential treatment options
September 25, 2018 - UC Davis researchers take critical step in developing more effective Salmonella vaccine
September 25, 2018 - Antibiotics best paediatric treatment for children’s chronic wet cough
September 25, 2018 - Looking beyond opioids: Stanford pain psychologist briefs Congress
September 25, 2018 - Organs actively fighting back against autoimmune diseases, finds study
September 25, 2018 - Lancaster professor aims to understand how genes affect smoking cessation
September 25, 2018 - Human-oriented perspective needed to better understand Parkinson’s disease
September 25, 2018 - Physical activity may have beneficial effects for people with rare Alzheimer’s disease
September 25, 2018 - FDA Updates on Valsartan Recalls
September 25, 2018 - 3-D-printed tracheal splints used in groundbreaking pediatric surgery
September 25, 2018 - Who is the designated driver, or proxy, for your health decisions?
September 25, 2018 - New chemo-optogenetic method enables multi-directional activity control of cellular processes
September 25, 2018 - Study explores link between genetic predisposition to Alzheimer’s and cardiometabolic risk factors
September 25, 2018 - NeoTract presents new clinical data from studies of UroLift System for patients with BPH
September 25, 2018 - Statins Improve Long-Term Survival After AAA Repair
September 25, 2018 - Novel brain network linked to chronic pain in Parkinson’s disease
September 25, 2018 - Researchers reassess negative pressure wound therapy as its benefit and harm remain unclear
September 25, 2018 - Older adults with ‘fall plan of care’ less likely to suffer fall-related hospitalizations
September 25, 2018 - FDA lifts partial clinical hold that paused enrollment of new patients in tazemetosta clinical trials
September 25, 2018 - IME Medical Electrospinning establishes state-of-the-art manufacturing lab facilities
September 25, 2018 - Phase 1 and 2 clinical trials of entrectinib drug in ROS1-positive NSCLC show promising results
September 25, 2018 - How to Protect Your Eyesight
September 25, 2018 - Novel approach allows researchers to define how cells in the retina respond to diabetes
September 25, 2018 - Columbia University announces winners of 2018 Louisa Gross Horwitz Prize
September 25, 2018 - Clinical trial investigators found non-compliant with requirement to report results on EU register
September 25, 2018 - Study analyzes quality of protein supplements in function of source, treatment and storage
September 25, 2018 - FDA grants Orphan Drug Designation to Myelo001 for treatment of Acute Radiation Syndrome
September 25, 2018 - U.S. Alzheimer’s Cases to Nearly Triple by 2060
September 25, 2018 - Improving cell replacement therapy for Parkinson’s disease
September 25, 2018 - Genervon reports new findings that drug candidate GM6 attenuates Alzheimer’s disease in mice model
September 25, 2018 - FDA approves new 5 mm diameter drug-eluting stent from Cook Medical
September 25, 2018 - New $17.8 million grant ensures USC at forefront of research on tobacco-related health risks
September 25, 2018 - Researchers analyze response to combination immunotherapy for patients with rare skin cancer
September 25, 2018 - Study sheds light on how brain protein may be involved neurodevelopmental disorders
September 25, 2018 - Where to draw the line on incentives
September 25, 2018 - Solid fuel use linked with increased risk of hospitalization or death from respiratory diseases
September 25, 2018 - ‘Trouble Brewing’ report highlights steps that governments can take to reduce alcohol-related harms
September 25, 2018 - Recurrence risk of VTE appears similar for patients with cancer and those with unprovoked VTE
September 25, 2018 - Global leaders must make bold commitments at first-ever UN tuberculosis summit
September 25, 2018 - Brief sleep intervention works long-term to prevent child obesity
September 25, 2018 - Vaping among kids and teens a growing concern
September 25, 2018 - Public launch of products and application solutions from Porvair Laboratory Division
September 25, 2018 - Harmful H. pylori may play a role in Parkinson’s disease
September 25, 2018 - Researchers develop way to measure different types of fear of falling in patients with Parkinson’s
September 25, 2018 - Fracture causes bone density losses throughout the body
September 25, 2018 - Researchers highlight potential therapy for treating rare, deadly blood-clotting disorder
September 25, 2018 - Hybrid theranostic complex shows high therapeutic efficacy against tumor cells
September 25, 2018 - FDA Issues Statement Reaffirming the Positive Benefit-Risk Profile of Nuplazid (pimavanserin) for Patients with Hallucinations and Delusions Associated with Parkinson’s Disease Psychosis
September 25, 2018 - Toxicological evaluation and dosimetry estimation of potential PET radiotracer
September 25, 2018 - 5 obstacles parents commonly face in child obesity treatment and how to overcome them
September 25, 2018 - Immunologist to study how Chikungunya causes devastating effects in older adults
September 25, 2018 - Rural borderland communities vulnerable to high stress impacting mental and physical health
September 25, 2018 - SNMMI announces recipients of 2018-2020 Wagner-Torizuka Fellowship
September 25, 2018 - Common painkiller not effective in controlling chronic pain after traumatic nerve injury
September 25, 2018 - New therapeutic vaccine helps immune cells fight HPV-related head and neck cancer
September 25, 2018 - Environmentally-induced gene activity influences IQ test performance
September 25, 2018 - Biogen and Eisai announce results of LTE Phase 1b study of aducanumab for treating MCI
September 25, 2018 - FDA Approves Copiktra (duvelisib) Capsules for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Follicular Lymphoma
September 25, 2018 - Medical device company settles US case over false claims
September 25, 2018 - Trying to get answers: One woman’s quest for a diagnosis
September 25, 2018 - Lung cancer patients treated with invasive surgery more likely to become chronic opioid users
September 25, 2018 - Oxford VR raises £3.2m to boost innovation in VR for mental health problems
September 25, 2018 - Gene therapy approach could help treat mitochondrial diseases
September 25, 2018 - Few Yogurt Products Qualify As Low-Sugar
September 25, 2018 - Eye disease can cause blindness, and it’s on the rise
September 25, 2018 - Pawnshop density linked to gun-related suicides, Stanford study finds
September 25, 2018 - Pioneering procedure for common prostate condition offered by The London Clinic
September 25, 2018 - Number of people with respiratory diseases likely to increase if UK air pollution remains unchecked
September 25, 2018 - FARXIGA receives positive results in Phase III DECLARE-TIMI 58 cardiovascular outcomes trial
September 25, 2018 - New program to reduce harmful stress effectively improves mood in cancer patients
September 24, 2018 - Florence’s Lingering Threat: Mold – Drugs.com MedNews
September 24, 2018 - For professional baseball players, faster hand-eye coordination linked to batting performance
September 24, 2018 - Bill for later school start times is defeated, but Stanford sleep specialist isn’t
September 24, 2018 - For Heart Failure Patients, Mitral Valve Procedure Improved Outcomes
September 24, 2018 - Successful recovery from addiction means more than achieving abstinence
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