Breaking News
December 15, 2018 - Young people suffering chronic pain battle isolation and stigma as they struggle to forge their identities
December 15, 2018 - Lifespan extension at low temperatures depends on individual’s genes, study shows
December 15, 2018 - New ingestible capsule can be controlled using Bluetooth wireless technology
December 15, 2018 - Researchers uncover microRNAs involved in the control of social behavior
December 15, 2018 - Research offers hope for patients with serious bone marrow cancer
December 15, 2018 - Link between poverty and obesity is only about 30 years old, study shows
December 15, 2018 - Mass spectrometry throws light on old case of intentional heavy metal poisoning
December 15, 2018 - BeyondSpring Announces Phase 3 Study 105 of its Lead Asset Plinabulin for Chemotherapy-Induced Neutropenia Meets Primary Endpoint at Interim Analysis
December 15, 2018 - Study finds that in treating obesity, one size does not fit all
December 15, 2018 - Tenacity and flexibility help maintain psychological well-being, mobility in older people
December 15, 2018 - Study reveals role of brain mechanism in memory recall
December 15, 2018 - High levels of oxygen encourage the brain to remain in deep, restorative sleep
December 15, 2018 - Experimental HIV vaccine strategy works in non-human primates, research shows
December 15, 2018 - Genetically modified pigs could limit replication of classical swine fever virus, study shows
December 15, 2018 - FDA Approves Herzuma (trastuzumab-pkrb), a Biosimilar to Herceptin
December 15, 2018 - Cost and weight-loss potential matter most to bariatric surgery patients
December 15, 2018 - Cancer Research UK and AstraZeneca open new Functional Genomics Centre
December 15, 2018 - New research lays out potential path for treatment of Huntington’s disease
December 15, 2018 - Prestigious R&D 100 Award presented to Leica Microsystems
December 15, 2018 - Study shows septin proteins detect and kill gut pathogen, Shigella
December 15, 2018 - Study sheds new light on disease-spreading mosquitoes
December 15, 2018 - 2017 Saw Slowing in National Health Care Spending
December 15, 2018 - Monitoring movement reflects efficacy of mandibular splint
December 15, 2018 - Study supports BMI as useful tool for assessing obesity and health
December 15, 2018 - Self-guided, internet-based therapy platforms effectively reduce depression
December 15, 2018 - Organically farmed food has bigger climate impact than conventional food production
December 15, 2018 - Faster, cheaper test has potential to enhance prostate cancer evaluation
December 15, 2018 - Researchers study abnormal blood glucose levels of patients after hospital discharge
December 15, 2018 - Swedish scientists explore direct association of dementia and ischemic stroke deaths
December 15, 2018 - Study finds 117% increase in number of dementia sufferers in 26 years
December 15, 2018 - Eczema Can Drive People to Thoughts of Suicide: Study
December 15, 2018 - Link between neonatal vitamin D deficiency and schizophrenia confirmed
December 15, 2018 - Nurse denied life insurance because she carries naloxone
December 15, 2018 - Ritalin drug affects organization of pathways that build brain networks used in attention, learning
December 15, 2018 - Research pinpoints two proteins involved in creation of stem cells
December 15, 2018 - Gut bacteria may modify effectiveness of anti-diabetes drugs
December 15, 2018 - Early physical therapy associated with reduction in opioid use
December 15, 2018 - Breast cancer protection from pregnancy begins many decades later, study finds
December 15, 2018 - How often pregnant women follow food avoidance strategy to prevent allergy in offspring?
December 15, 2018 - Using machine learning to predict risk of developing life-threatening infections
December 15, 2018 - How imaginary friends could boost children’s development
December 15, 2018 - Folate deficiency creates more damaging chromosomal abnormalities than previously known
December 15, 2018 - Study provides new insights into molecular mechanisms underlying role of amyloid in Alzheimer’s disease
December 15, 2018 - For the asking, a check is in the mail to help pay for costly drugs
December 15, 2018 - UA scientists uncover biological processes leading to rare brain disorder in babies
December 15, 2018 - The largest database on industrial poisons
December 15, 2018 - ESMO Immuno-Oncology Congress showcases novel technologies set to benefit many cancer patients
December 15, 2018 - Ovid Therapeutics Announces Plans to Move into a Phase 3 Trial in Pediatric Patients Based on End-of-Phase 2 Meeting for OV101 in Angelman Syndrome
December 15, 2018 - Left ventricular noncompaction – Genetics Home Reference
December 15, 2018 - Children’s sleep not significantly affected by screen time, new study finds
December 15, 2018 - When should dementia patients stop driving? A new guidance for clinicians
December 15, 2018 - Researchers use INTEGRA’s VIAFLO 96/384 to streamline the experimental workflow
December 15, 2018 - Researchers discover protein involved in nematode stress response
December 15, 2018 - Cancer patients have greater risk of developing shingles, study shows
December 14, 2018 - UAlberta scientists identify biomarkers for detecting Alzheimer’s disease in saliva samples
December 14, 2018 - Study uncovers link between tube travel and spread of flu-like illnesses
December 14, 2018 - Caffeine plus another compound in coffee may fight Parkinson’s disease
December 14, 2018 - GW researchers review studies on treatments for prurigo nodularis
December 14, 2018 - Lack of peds preventive care ups unplanned hospital admissions
December 14, 2018 - Miscarriage: When Language Deepens Pain
December 14, 2018 - New method helps better understand pathological development of ALS
December 14, 2018 - Intellectually active lifestyle confers protection against neurodegeneration in Huntington’s patients
December 14, 2018 - Mammalian collagen nanofibrils become stronger and tougher with exercise
December 14, 2018 - Considerable Morbidity, Mortality Due to Animal Encounters
December 14, 2018 - Researchers find inhibiting one protein destroys toxic clumps seen in Parkinson’s disease
December 14, 2018 - How early physical therapy can lessen the long-term need for opioids
December 14, 2018 - Depression, suicide rates highest in Mountain West states
December 14, 2018 - New model could cure the potential to underestimate how quickly diseases spread
December 14, 2018 - Exercise-induced hormone activates cells critical for bone remodeling in mice
December 14, 2018 - Researchers discover new mechanism behind spread of malignant pleural mesothelioma
December 14, 2018 - Health Tip: Celebrate a Healthier Holiday
December 14, 2018 - Scalpel-free surgery enhances quality of life for Parkinson’s patients, study finds
December 14, 2018 - Early physical therapy can reduce risk, amount of long-term opioid use | News Center
December 14, 2018 - Genetic marker, predictor of early relapse in common childhood cancer discovered
December 14, 2018 - Study could lead to a potential new way of treating sepsis
December 14, 2018 - New protein complex helps embryonic stem cells to maintain their indefinite potential
December 14, 2018 - Salk professor receives $1.8 million from NOMIS Foundation for research on mechanisms to promote health
December 14, 2018 - New discovery will improve the safety and predictability of CRISPR
December 14, 2018 - Geneticists discover how sex-linked disorders arise
December 14, 2018 - New method to visualize small-molecule interactions inside cells
Specific bacteria in the intestines can improve response rate to cancer immunotherapy

Specific bacteria in the intestines can improve response rate to cancer immunotherapy

image_pdfDownload PDFimage_print

In the Jan. 5, 2018 issue of Science, researchers from the University of Chicago Medicine show that specific strains of commensal bacteria – the swarms of microorganisms naturally dwelling in the intestines – can improve the response rate to immunotherapy for patients being treated for advanced melanoma.

Although these immune system boosting drugs have revolutionized treatment of certain cancers, only about 35 percent of melanoma patients who receive them get a significant benefit. In their paper, “The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients,” the UChicago researchers demonstrate that several defined bacterial species, including Bifidobacterium longum, Collinsella aerofaciens and Enterococcus faecium, were much more prevalent in the intestines of the 16 patients who responded to treatment (38 percent) than in the 26 patients (62 percent) who did not.

The presence of these specific bacteria in the intestine appears to enhance T-cell infiltration into the tumor microenvironment and augment T-cell killing of cancer cells, increasing the odds of a vigorous and durable response.

The strong correlation between specific gut bacteria and a clinical response to anti-PD-1 immunotherapy suggests “a causal relationship,” said study director Thomas Gajewski, MD, PhD, the AbbVie Foundation Professor of Cancer Immunotherapy at the University. “Specific bacteria clearly contribute to improved anti-tumor immunity in patients. The gut microbiota has a more profound effect than we previously imagined.”

The current study follows a November 2015 Science paper from Gajewski’s laboratory, one of the first to connect the presence of specific intestinal bacteria to greater potency for immunotherapy. These initial papers showed that the composition of the gut microbiome can influence how well these cancer immunotherapies work in mice.

Although the earlier mouse data was striking, “we knew there were multiple barriers that can decrease the odds that immunotherapy will work,” Gajewski said. “We initially thought the microbiome was a minor component. But in our current study, these bacteria were a very strong predictor of who would respond.”

The current paper focuses on humans – 42 patients going through treatment for metastatic melanoma. The researchers collected stool samples from each patient prior to treatment. Thirty-eight patients then received an anti-PD-1 drug, so-called “checkpoint inhibitors such as nivolumab or pembrolizumab. Four more patients received a related drug, anti-CTLA4 (ipilimumab).

The researchers focused on eight bacterial species that were more prevalent in patients who did respond to therapy as well as two species that were more abundant in patients who did not respond. Because of bacterial variations, the team used three different methods to determine the genetic sequences of the microbes.

Patients with a higher ratio of the “beneficial” bacteria to “non-beneficial” bacteria all showed a clinical response, meaning a reduction in tumor size.

The researchers then ran a smaller experiment in reverse. They collected fecal bacteria from three human subjects who responded favorably to treatment, and three who did not respond. They transferred those bacteria into the intestines of germ-free mice. Two weeks later they implanted melanoma cells in the mice.

Two out of three mouse groups given bacteria from human responders had slow-growing tumors and two out of three with fecal material from human non-responders had fast-growing tumors. Mice treated with PD-1-blocking drugs only showed tumor shrinkage if they had microbiota from responding patients.

Two other research teams found similar results but pinpointed different bacteria. A group from the Gustave Roussy Cancer Campus in Villejuif, France, suggested that Akkermansia muciniphila contributed to the antitumor effect of the microbiome. Another team from MD Anderson Cancer Center in Houston, Texas, focused on Faecalibacterium and Clostridiales.

“Our results strongly suggest that the microbiota is a major factor, a gatekeeper for the immune response against a tumor,” Gajewski said. “Without microbial support, the immune response just never quite gets going.”

“Our results have pushed us in two directions,” he added. “We have to start experimenting with probiotics as a way to enhance immunotherapy. We hope to launch a clinical trial using Bifidobacteria in 2018.”

They also hope to expand the list of both beneficial and potentially harmful gut bacteria in cancer patients and to identify the mechanisms by which bacteria influence the immune system’s response to cancer control.

“Our current results,” the authors conclude, “open the avenue for integrating commensal microbial composition along with tumor genomes and germline genetics into a multi-parameter model for maximizing the ability to predict which patients are likely to respond to immunotherapies such as anti-PD-1.”

Source:

http://www.uchospitals.edu/

Tagged with:

About author

Related Articles