Breaking News
January 18, 2019 - Let’s map our DNA and save billions each year in health costs
January 18, 2019 - AI demonstrates potential to identify irregular heart rhythms as well as humans
January 17, 2019 - Study shows link between air pollution and increased risk of sleep apnea
January 17, 2019 - Neck-strengthening exercises can protect athletes from concussions
January 17, 2019 - Computer model shows how to better control MRSA outbreaks
January 17, 2019 - Pain is unpleasant, and now scientists have identified the set of responsible neurons
January 17, 2019 - CUIMC Celebrates 2018-2019
January 17, 2019 - Study reveals potential pathway for endothelial cells to avoid apoptosis
January 17, 2019 - Hamilton Storage launches LabElite DeCapper SL to expand LabElite product family
January 17, 2019 - Location of epigenetic changes co-locate with genetic signal causing psychartric disorder
January 17, 2019 - Researchers awarded 6.1 million euros to address female fertility problems
January 17, 2019 - Counseling appointments fail to reduce weight gain during pregnancy, shows study
January 17, 2019 - Contraceptive patch that could provide 6 months of contraception within seconds
January 17, 2019 - Yeast model may pave way for development of novel therapies for metabolic disorders
January 17, 2019 - Study determines impact of antibiotic perturbation of the gut microbiome on skeletal health
January 17, 2019 - Cardiometabolic Risk Up With Tourette, Chronic Tic Disorder
January 17, 2019 - Hong Kong scientists claim ‘broad-spectrum’ antiviral breakthrough
January 17, 2019 - Researchers discover the brain cells that make pain unpleasant | News Center
January 17, 2019 - Hepatitis Is Common in New Cancer Patients
January 17, 2019 - Podcast: KHN’s ‘What The Health?’ Drug Prices Are Rising Again. Is Someone Going To Do Something About It?
January 17, 2019 - Smoking significantly increases your biological age, study shows
January 17, 2019 - B-group vitamins may be beneficial for people with first episode psychosis
January 17, 2019 - Researchers demonstrate how manganese produces parkinsonian syndrome
January 17, 2019 - Researchers suggest link between personality type and attitude towards others’ bodies
January 17, 2019 - Mutant mice administered with cocaine failed to exhibit hyperactivity, shows study
January 17, 2019 - Health Tip: Understanding a Heart Murmur
January 17, 2019 - Gut protein mutations shield against spikes in glucose
January 17, 2019 - Engineered immune cells target broad range of pediatric solid tumors in mice | News Center
January 17, 2019 - Study finds link between high pesticide exposure and poor sense of smell among farmers
January 17, 2019 - Many cancer patients have undiagnosed hepatitis
January 17, 2019 - New study finds only 13% of outpatient antibiotic prescriptions to be appropriate
January 17, 2019 - Stem cell-based approach to diabetes offers hope for treatment
January 17, 2019 - New project receives €8.65 million from EU and Canada to ease genomic, health data sharing
January 17, 2019 - Improvements in pharmacological study to fight cognitive impairment in schizophrenia
January 17, 2019 - Study looks at trends over time in oral antibiotic prescribing by dermatologists
January 17, 2019 - Most substance use disorder treatment facilities do not offer medication treatment
January 17, 2019 - Multiple sclerosis could benefit from stem cell therapy
January 17, 2019 - Researchers manipulate T cells to improve transplant success
January 17, 2019 - Put away your rulers and reach for your phone
January 17, 2019 - Mindfulness linked with fewer menopausal symptoms
January 17, 2019 - Integrated care to women with PMADs offered at several levels
January 17, 2019 - Researchers identify MANF as a rejuvenating factor in parabiosis
January 17, 2019 - Truncal mutations study suggests new direction in origins of cancer
January 17, 2019 - Beckman Coulter launches new ClearLLab 10C System for clinical flow cytometry lab
January 17, 2019 - Effects of linoleic acid on the body are largely dependent on genes, shows study
January 17, 2019 - Pre-injury exercise reduces damage to both muscles and nerves, study finds
January 17, 2019 - Minimizing Antibody Size to Maximize Research Potential
January 17, 2019 - Research finds large genome in tiny forest defoliator
January 17, 2019 - Technology helps reduce the yearning for unhealthy food
January 17, 2019 - Imec develops prototype cardiovascular device
January 17, 2019 - New Drug Application for Insomnia Disorder Treatment Lemborexant Submitted in the United States
January 17, 2019 - What you should know about teeth whitening
January 17, 2019 - Why Older Adults Should Eat More Protein (And Not Overdo Protein Shakes)
January 17, 2019 - Colorectal cancer mortality rates predicted to increase globally
January 17, 2019 - Scientists discover mutational signatures of tumor hypoxia
January 17, 2019 - New evidence shows how fever alters immune cells
January 17, 2019 - Researchers find new class of blood pressure-regulating peptides in vampire bat venom
January 17, 2019 - Promega to exhibit new Maxwell RSC48 platform at 2019 Festival of Genomics
January 17, 2019 - Study pinpoints immune cells that could be key to tackling hypertension
January 17, 2019 - Couples Intervention May Aid Partners of Diabetes Patients
January 17, 2019 - Your weight history may predict your heart failure risk
January 17, 2019 - Explore a cornucopia of accomplishments in prematurity research
January 17, 2019 - New study identifies four characteristics that predict severity of postpartum depression
January 17, 2019 - AHF urges United Nations to follow own mandate for protecting Ebola response efforts
January 17, 2019 - New, scalpel-free treatment for reducing Parkinson’s tremor gets FDA approval
January 17, 2019 - Neurobiologists uncover key component of how the human brain marks time
January 17, 2019 - LifeTime receives fund to develop a plan to embed its vision for healthier future
January 17, 2019 - WTC first responders at higher risk for head and neck cancers, study finds
January 17, 2019 - New NSF funded study may help physicians decrease brain injury deaths
January 17, 2019 - Ham bones contain peptides that could have cardioprotective effects
January 17, 2019 - Research finds how Candida albicans adapt to low oxygen levels to cause infection
January 17, 2019 - Cobra Biologics announces appointment of Dr Darrell Sleep as Director of Innovation
January 17, 2019 - Cellular protein that interacts with viruses appears to enable infection process of Zika virus
January 17, 2019 - Opioids Now More Deadly for Americans Than Traffic Accidents
January 17, 2019 - Women who start periods early are at greater risk of cardiovascular problems
January 17, 2019 - The brain-circuitry clash that keeps you from diving into that plate of ribs when you’re dining with royalty
January 17, 2019 - Poo transplant can successfully treat patients with ulcerative colitis
January 17, 2019 - Study suggests key role for glial cells in Parkinson’s disease
January 17, 2019 - Educational videos in clinical settings increase HPV vaccination rates among adolescents
January 17, 2019 - Better understanding of aggressive brain tumour
Prostate cancer’s gene-determined ‘immune landscape’ dictates tumor progression

Prostate cancer’s gene-determined ‘immune landscape’ dictates tumor progression

image_pdfDownload PDFimage_print

The field of immunotherapy – the harnessing of patients’ own immune systems to fend off cancer – is revolutionizing cancer treatment today. However, clinical trials often show marked improvements in only small subsets of patients, suggesting that as-yet unidentified variations among tumors result in distinct paths of disease progression and response to therapy.

Now, researchers at the Cancer Center at Beth Israel Deaconess Medical Center (BIDMC) have demonstrated that genetic variations driving prostate cancer determine the composition of the immune cells that have been found to infiltrate primary prostate tumors. These immune cells, in turn, dictate tumor progression and response to treatment. The data, published in Nature Medicine, suggest that profiling patients’ tumors based on this new information could lead to more successful clinical trials and tailored therapies for patients.

“We observed that specific genetic events resulted in striking differences in the composition of immune cells present in and around the tumor – results with important therapeutic implications,” said senior author Pier Paolo Pandolfi, MD, PhD, Director of the Cancer Center and Cancer Research Institute at BIDMC. “Our data may be especially relevant for tailoring immunological therapies and for identifying responsive-patient population.”

The third leading cause of cancer-related death in U.S. men, prostate cancer, is linked to a number of diverse genetic mutations that drive the disease. For example, the loss of the tumor suppressor gene PTEN is a frequent event in prostate cancer and is well known to promote the disease in combinations with a plethora of other mutations. Researchers also know that the tumor’s microenvironment – the blood vessels, immune cells, signaling molecules and other factors that surround the tumor – plays an important role in tumor progression and response to therapy.

Pandolfi’s team – including lead author, Marco Bezzi, a post-doctoral fellow in Pandolfi’s lab – engineered mice models to represent four distinct known genetic variations of human prostate cancer. The models lacked either Pten alone or in combination with other genetic alterations known to drive the disease. When the team analyzed the tumors from these mice, they saw profound differences in the types and relative numbers of the immune cells that had accumulated in and around the tumor, what they call the tumors’ “immune landscape”.

For example, specific immune landscapes tumors from the genetic model lacking both Pten and the tumor suppressor gene called Trp53 demonstrated an increased accumulation of myeloid cells, the immune cells that mediate immunosuppression. In stark contrast, tumors from the genetic model lacking Pten and a different tumor suppressor gene called PML lacked intratumoral immune infiltration; that is, the researchers observed no immune cells at all in these tumors, which the scientists dubbed “cold,” or “immune-deserts.” All four mouse models analyzed presented very distinctive immune landscapes and these differences were maintained and exacerbated over time.

The research team also demonstrated that these differences in immune cell composition were directly dictated by the tumors themselves because of their genetic variations. Different tumors, they observed, secreted distinct chemical attractants, which in turn recruited – or didn’t recruit, in the case of the immune-desert tumors – different immune cell types into the tumor. Pandolfi and colleagues further demonstrated that these differences hold true in human prostate cancer. Critically, the immune cells recruited to the tumors were found to be essential in supporting the growth and progression of these tumors.

“We observed that when present, these infiltrating immune cells were required for the tumor to thrive and found therapies to block their recruitment to be effective,” said Bezzi. “On the other hand, the cancer genotype characterized by the so-called ‘immune desert’ phenotype, did not respond to such therapies. On this basis, we can predict the tumor response to immunotherapies and tailor treatment modalities to effectively impact tumors that are otherwise extremely aggressive,” he said.

Thus, because immune cells interact with and also affect tumor response to therapy, these findings may be especially relevant for the development of more precise and effective combinations of immunotherapies and targeted therapies on the basis of the cancer genetic makeup.

“These profound differences in immunological landscapes among various cancer genotypes further highlight the need to thoroughly investigate and integrate genotypes and immune-phenotypes in the context of exploratory cancer treatments in both preclinical and clinical settings,” said Pandolfi.​​

Source:

http://www.bidmc.org/News/PRLandingPage/2018/January/Pandolfi-Bezzi.aspx

Tagged with:

About author

Related Articles