Breaking News
August 20, 2018 - Medicine on the front line to be presented at Medical Innovation 2018
August 20, 2018 - Harbour Biomed and Kelun-Biotech collaborate to develop, commercialize anti-PD-L1 antibody
August 20, 2018 - The man who sold America on vitamin D — and profited in the process
August 20, 2018 - Finding the light in antimicrobials
August 20, 2018 - Unique pain program helps surgical patients wean off opioids safely and effectively
August 20, 2018 - Strawberries could mitigate colonic inflammation
August 20, 2018 - FDA Accepts New Drug Application (NDA) to Review Midazolam Nasal Spray, an Investigational Product for the Acute Treatment of Seizure Clusters
August 20, 2018 - Using Facebook to help young adults quit smoking
August 20, 2018 - ‘Liquid biopsy’ predicts lymphoma therapy success within days | News Center
August 20, 2018 - 5 Questions with Jordan Orange, Chair of Pediatrics
August 20, 2018 - New assay may help improve both sarcoma diagnosis and treatment
August 20, 2018 - New class of insect repellents to fight against mosquito-borne diseases
August 20, 2018 - ACA Coverage Gains Include Workers Without Insurance
August 20, 2018 - 3-D printed biomaterials for bone tissue engineering
August 20, 2018 - Prenatal exposure to acute stress can affect cognitive function in children of low-income households
August 20, 2018 - New study examines scope of state policies targeting drug use by pregnant women
August 20, 2018 - Researchers find long-term structural, functional brain abnormalities in individuals with AUDs
August 20, 2018 - Shortage of insurance fraud cops sparks campaign debate
August 20, 2018 - Researchers find STAT3 as therapeutic target for chronic active EBV infection
August 20, 2018 - Health Tip: Keep Diabetic Feet Healthier
August 20, 2018 - FDA approves brain stimulation device for OCD
August 20, 2018 - NYU Langone’s Perlmutter Cancer Center expands Blood and Marrow Transplant Program
August 20, 2018 - New drug shows potential to prevent painful side effect of therapy
August 20, 2018 - RDMD raises $3 million in seed funding to accelerate rare disease research, drug development
August 20, 2018 - Illicit drug use is higher during celebratory events, may be worse than previously thought
August 20, 2018 - Exploring the relationship between fever and cancer incidence
August 20, 2018 - Study reveals how socioeconomic status affects racial, ethnic disparities in childhood cancer survival
August 20, 2018 - Brain tumors trap immune cells needed to fight cancer in the bone marrow, finds research
August 20, 2018 - Three factors that contribute to physician burnout
August 20, 2018 - Babies dependent on opioids need touch, not tech
August 20, 2018 - Understanding How Antibodies Shape the Gut Microbiome
August 20, 2018 - Cara Therapeutics Doses First Patient in Second Pivotal Phase 3 Efficacy Trial of Korsuva (CR845/difelikefalin) Injection in Hemodialysis Patients with Chronic Kidney Disease-Associated Pruritus
August 20, 2018 - Kidney transplant chains more effective in saving lives
August 20, 2018 - Study unravels cellular and molecular mechanisms behind dermal condensate formation
August 20, 2018 - New integrated gene logic-chips could have great value in medical care
August 20, 2018 - FDA Advisory Committee Recommends Approval of Paratek’s Omadacycline
August 20, 2018 - Total, open repairs decline for abdominal aortic aneurysms
August 20, 2018 - Novel system can pinpoint ingestible implants inside the body using wireless signals
August 20, 2018 - Infection rates of high risk oral HPV in England found to be lower than expected
August 20, 2018 - Making robots as valuable and trustworthy assistants for medical therapies
August 20, 2018 - Patients with low-risk blood clots can be better treated at home than at hospital
August 20, 2018 - Passive smoking exposure among kids greatly increases COPD risk late in life
August 20, 2018 - Primary Care Provider Burnout Rate Low in Small Practices
August 20, 2018 - Discovery presents treatment hope for Alzheimer’s and other neurodegenerative diseases
August 20, 2018 - Stroke patients appear to receive better care at teaching hospitals with less chance of readmission
August 20, 2018 - Distinct origin of ADHD identified In children with history of traumatic brain injury
August 20, 2018 - AHA: Wildfire Smoke Threatens Health of Those Near and Far
August 20, 2018 - Here’s a mental health workout that’s as simple as ABC
August 20, 2018 - Newly discovered cytoskeleton utilized by cancer cells for survival
August 19, 2018 - Bifidobacteria supplement colonizes gut of breastfed infants
August 19, 2018 - Why patients with Alzheimer’s markers never develop the condition
August 19, 2018 - ACA’s Medicaid expansion associated with increase in prescriptions for opioid use disorder treatment
August 19, 2018 - Important factor may be missing in models used to predict spread of epidemics from climate change
August 19, 2018 - Indian-Americans have fewer sudden infant deaths, study finds
August 19, 2018 - Experts advise against universal genomic screening of newborns
August 19, 2018 - New trial to investigate whether weight loss before conception can make mom and baby healthier
August 19, 2018 - Sun Pharma Announces FDA Approval of Cequa (cyclosporine) Ophthalmic Solution to Treat Dry Eye Disease
August 19, 2018 - Researchers examining Parkinson’s resilience
August 19, 2018 - HPI, INTEGRIS and USPI enter into agreement to offer patients more choice, flexibility of care
August 19, 2018 - Researchers find mechanism that prepares brain to replicate repeated actions
August 19, 2018 - Those who are emotionally stable when young may remain the most stable as they age
August 19, 2018 - URI professor develops simpler and quicker method for detecting impurity in heparin
August 19, 2018 - Mayo Medical Laboratories and NDSC collaborate to develop new patient blood-management solution
August 19, 2018 - Insight into endocrine cancers and treatment options
August 19, 2018 - HPV Legislation Doesn’t Impact Teen Sexual Behaviors
August 19, 2018 - Exenatide treatment alleviated symptoms of depression in patients
August 19, 2018 - Tufts researchers win grant to study integration of genomic sequencing into neonatal care
August 19, 2018 - Novel finger-prick test can help prevent toxoplasmosis
August 19, 2018 - Cosmetic Procedures Boost Well-Being, Poll Shows
August 19, 2018 - Responsive parenting intervention results in lower BMIs through age three
August 19, 2018 - Anticancer drugs can help plants to battle infection
August 19, 2018 - Sunscreen from bathers releases significant quantities of polluting titanium dioxide into the sea
August 19, 2018 - Case Western Reserve gets three-year grant to enhance food systems in Cleveland neighborhoods
August 19, 2018 - Teenagers can thank their parents’ positive attitude for avoiding obesity
August 19, 2018 - Body mass index positively linked with blood pressure
August 19, 2018 - New tool fills gap in Small Molecules market
August 19, 2018 - Study compares survival outcomes in rural and urban cancer patients enrolled in clinical trials
August 19, 2018 - Researchers develop molecular matrix that delivers healing stem cells to injured elderly muscles
August 19, 2018 - Teva and Regeneron Announce Positive Topline Phase 3 Fasinumab Results in Patients with Chronic Pain from Osteoarthritis of the Knee or Hip
August 19, 2018 - New study pinpoints ways to improve quality of food and nutrition research
Precancerous colon polyps in Lynch syndrome patients display immune activation

Precancerous colon polyps in Lynch syndrome patients display immune activation

image_pdfDownload PDFimage_print

Colon polyps from patients with Lynch syndrome, a hereditary condition that raises colorectal cancer risk, display immune system activation well before cancer development, according to research from The University of Texas MD Anderson Cancer Center. The preclinical research challenges traditional models of cancer immune activation and suggests immunotherapy may be useful for colorectal cancer prevention in certain high-risk groups.

The findings, published in JAMA Oncology, will be presented today at the American Association for Cancer Research Annual Meeting 2018 in Chicago by Kyle Chang, graduate research assistant.

Immune checkpoint inhibitors targeting PD-1, such as pembrolizumab and nivolumab, have been successful in treating colorectal cancers with deficiencies in DNA mismatch repair (MMR). These tumors accumulate large numbers of genetic mutations and mutant proteins, or neoantigens, which are thought to stimulate an immune response, making them more susceptible to checkpoint blockade therapy.

“Our question was how this worked in premalignancy,” said senior author Eduardo Vilar-Sanchez, M.D., Ph.D., assistant professor of Clinical Cancer Prevention and Gastrointestinal (GI) Medical Oncology. “Can we apply checkpoint inhibitors or checkpoint inhibitor strategies to prevent MMR-deficient colorectal cancer?”

Lynch syndrome (LS), which is caused by inherited mutations in MMR, provides the perfect context in which to study early immune activation and explore the potential use of checkpoint inhibitors in a prevention setting, explained Vilar-Sanchez. Over 1 million people in the U.S. are affected by LS, the most common hereditary colorectal cancer syndrome.

In the study, the researchers analyzed gene expression to characterize the immune profile in 11 polyps and three early-stage tumors from 14 patients with LS. As a control, the researchers also analyzed 17 polyps from patients with Familial Adenomatous Polyposis (FAP), a hereditary colorectal cancer syndrome which does not exhibit MMR deficiencies.

The resulting profiles revealed increased expression of several markers of immune activation, including CD4 T-cells, proinflammatory molecules and checkpoint molecules, such as PD-L1 and LAG-3, in LS polyps compared to FAP polyps. However, contrary to traditional models of immune activation, the observed immune profiles were independent of the rate of mutations or neoantigens present in the sample.

“To our surprise, our findings don’t follow the standard model. The majority of premalignant lesions do not have an excessive increase in mutations or neoantigens,” said Vilar-Sanchez. “However, we observed there is already immune activation, meaning the activation precedes the development of the mutations.”

The findings suggest a baseline level of immune activation exists in precancerous polyps, which may prime them for susceptibility to checkpoint blockade, explained Vilar-Sanchez.

Future work will be necessary to clarify the mechanism by which this immune activation occurs, as the current study was observational in nature. The researchers hope to initiate clinical studies to investigate the use of checkpoint blockade strategies for preventing colorectal cancer in high-risk groups, such as those with LS.

“Lynch syndrome patients have a strong immune activation in the colon, and that immune activation can be exploited for preventive purposes,” said Vilar-Sanchez. “I think our data provide the information needed to launch studies to use checkpoint inhibition in the setting of prevention.”

Source:

https://www.mdanderson.org/newsroom/2018/04/precancerous-colon-polyps-in-patients-with-lynch-syndrome-exhibit-immune-activation.html

Tagged with:

About author

Related Articles