Breaking News
June 20, 2018 - Simple cognitive task after brain injury improves memory function, study finds
June 20, 2018 - Clinical trial targets metastatic colorectal cancer with new combination therapy
June 20, 2018 - Researchers discover pesticide-free way to limit mosquitoes and reduce spread of West Nile virus
June 20, 2018 - Persistent psychological stress contributes to development and progression of vision loss
June 20, 2018 - Study introduces novel strategy to obtain reasonable drug cost estimates for cost-effectiveness analyses
June 20, 2018 - Does Salt Water Help Your Cut? And Other Health Myths of Summer
June 20, 2018 - Scientists help identify genetic markers for prostate cancer in global DNA download
June 19, 2018 - Common ingredient in toothpaste and hand wash could contribute to antibiotic resistance
June 19, 2018 - WHO launches multiyear campaign to eliminate use of trans fat
June 19, 2018 - Scientists could build better drugs by learning from bacteria-derived molecules
June 19, 2018 - Comparative silence between firing spikes of neurons reveals what they are really up to
June 19, 2018 - JAK inhibitors associated with aggressive lymphoma
June 19, 2018 - SetPoint announces positive long-term results of bioelectronic medicine to treat rheumatoid arthritis
June 19, 2018 - Hypnosis may help reduce fear, anxiety in children undergoing treatment for cancer
June 19, 2018 - Scientists point to potentially promising treatment target for deadly brain cancers
June 19, 2018 - After opioid overdose, only 30 percent get medicine to treat addiction
June 19, 2018 - Patients with mild Alzheimer’s disease over age 65 continue to derive benefit from DBS-f treatment
June 19, 2018 - Microbiotica partners with University of Adelaide to develop defined bacterial product for ulcerative colitis
June 19, 2018 - Paratek Presents New Analysis from Combined Phase 3 Skin Infection Studies Highlighting Efficacy of Omadacycline in Treating Drug Resistant S. aureus
June 19, 2018 - Autism is not linked to eating fish in pregnacy
June 19, 2018 - Scientists create universal assembly method to enhance cancer therapy and diagnostics
June 19, 2018 - FDA provides guidance on Novus Therapeutics’ development path for OP-02 to treat otitis media
June 19, 2018 - Scientists discover new mechanism controlling multiple sclerosis risk
June 19, 2018 - Award granted to Neem Biotech to develop antimicrobial intervention for chronic lung infections
June 19, 2018 - Study finds combined risk of death and developing cancer to be lowest in light drinkers
June 19, 2018 - Novel app teaches users how to stop life-threatening bleeding and save lives
June 19, 2018 - Single blood sample can provide adequate confirmation of diabetes
June 19, 2018 - New stimulation method increases hope for improving disorders of consciousness
June 19, 2018 - FDA Issues Complete Response Letter for Duobrii (halobetasol propionate and tazarotene) Lotion
June 19, 2018 - Defining the biology of autism
June 19, 2018 - Researchers use optogenetics to shape tissues
June 19, 2018 - Scientists discover genetic causes underlying group of related infant cancers
June 19, 2018 - Innovative digital home testing kit benefits patients with kidney conditions
June 19, 2018 - New guidance on selection and evaluation of wearable devices for use in regulatory clinical trials
June 19, 2018 - Researchers understand the role of brain’s ‘reward circuit’ in autism spectrum disorder
June 19, 2018 - Researchers propose new strategy to combat micro-pollutants in water
June 19, 2018 - Illicit Opioid Trade Up With Restrictions on Hydrocodone
June 19, 2018 - New 3-D imaging analysis technique could lead to improved arthritis treatment
June 19, 2018 - Study finds increased risk of mortality in people with cold agglutinin disease in five years after diagnosis
June 19, 2018 - Psychologists can play important role in treating alcohol problems
June 19, 2018 - Study finds elevated risk of congenital defects in lithium-exposed infants
June 19, 2018 - Test-Taking Can Be Tough for Kids With Vision Problems
June 19, 2018 - Injections for knee osteoarthritis—’subtle but significant’ impact of revisions in clinical practice guidelines
June 19, 2018 - Researchers develop new approach to assess effectiveness of Men B vaccine
June 19, 2018 - Study shows link between financial literacy and hospitalization risk in older adults
June 19, 2018 - If you’ve got hep C, spitting can be a felony
June 19, 2018 - New study examines how the brain plays role in rheumatoid arthritis inflammation
June 19, 2018 - Researchers discover new defense mechanism against oxygen radicals
June 19, 2018 - WVU researcher aims to produce updated whooping cough vaccine
June 19, 2018 - Scientists develop novel computational framework to support personalized cancer treatment
June 19, 2018 - Rate of dementia on the decline—but beware of growing numbers
June 19, 2018 - Microglia play protective role in response to retinal detachment, shows study
June 19, 2018 - Technology breakthrough could enable detection of fetal genetic abnormalities in early pregnancy
June 19, 2018 - Novel chip can be used to identify rhinovirus strains as cause of asthma
June 19, 2018 - Effects of in vitro fertilization depend on genetic variation inherited from parents
June 19, 2018 - Heart attack patients unable to resume work report depression and financial hardship
June 19, 2018 - Study combines gene editing and stem cell technologies to predict person’s risk for heart disease
June 19, 2018 - Weight loss of 20% or greater results in better outcomes for overweight, obese adults with knee osteoarthritis
June 19, 2018 - Alnylam Reports Updated Positive Results from Phase 1/2 Study of Lumasiran in Patients with Primary Hyperoxaluria Type 1 (PH1)
June 19, 2018 - Study predicts most people with earliest Alzheimer’s signs won’t develop dementia associated with the disease
June 19, 2018 - Abnormal sleep duration linked to metabolic syndrome in new study
June 19, 2018 - Researchers develop new method to preserve fertility in boys with prepubertal cancer
June 19, 2018 - Late onset of diabetes could be indicative of pancreatic cancer
June 19, 2018 - WHO releases new International Classification of Diseases (ICD-11)
June 19, 2018 - Skin tone makes big difference in diagnosis and treatment of dermatologic conditions
June 19, 2018 - After addiction, the long road back to good health
June 19, 2018 - High blood pressure could be an early sign of dementia
June 19, 2018 - Innovative drugs and new European treatment guidelines refine, improve MS therapy
June 19, 2018 - BIDMC scientists develop new tool to benefit patients with HCV-associated liver failure
June 19, 2018 - Diabetes diagnosis may come with increased risk of pancreatic cancer for African-Americans, Latinos
June 19, 2018 - Personalized Goals, Cash Motivate Heart Patients to Exercise
June 19, 2018 - Nipah Virus (NiV) | CDC
June 19, 2018 - Genomics offers new treatment options for infants with range of soft tissue tumors
June 18, 2018 - Study shows how moderate consumption of alcohol can protect the heart
June 18, 2018 - Gene editing technology predicts heart disease risk
June 18, 2018 - Who Will and Who Won’t Get the Flu?
June 18, 2018 - Research shows effective responses to online feedback
June 18, 2018 - Scientists to focus on big data and genetics to identify risk factors for dementia
June 18, 2018 - Ultrasound-based technology for assessing overweight adolescents with liver disease
June 18, 2018 - Osteochondral knee defect treated using cell technology
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