Breaking News
December 19, 2018 - Energy costs, social isolation contribute to health risk of older adults in extreme weather
December 19, 2018 - Potential combination therapy against rare disease of the bone marrow could improve treatment
December 19, 2018 - UC San Diego Health offers new DRG stimulation device for phantom limb pain
December 19, 2018 - Study examines relationship between growth restriction and risk of childhood mortality
December 19, 2018 - New study provides insights on increased risk of suicide in young patients visiting ED
December 19, 2018 - AHA: Thyroid Problems Linked to Worsening Heart Failure
December 19, 2018 - World-first coeliac disease vaccine enters Phase 2 trials
December 19, 2018 - RNA sequencing offers novel insights into the microbiome
December 19, 2018 - A promising, effective vaccine for common respiratory disease
December 19, 2018 - Protein may slow progression of emphysema, study finds
December 19, 2018 - Studying atrial fibrillation — and exploring new frontiers in precision health
December 19, 2018 - A New Way To Get College Students Through A Psychiatric Crisis — And Back To School
December 19, 2018 - Optum, UnitedHealthcare take action to help people affected by North Carolina winter storms
December 18, 2018 - Weight change in middle-aged, elderly Chinese Singaporeans related to increased risk of death
December 18, 2018 - Immune cells sacrifice themselves to protect us from invading bacteria
December 18, 2018 - Watching brain cells fire, with a twist of gravitational waves
December 18, 2018 - 2018 in Review
December 18, 2018 - Getting the Most Out of the CLARITY Technique
December 18, 2018 - NVF shoes provide a viable option for track and road racing
December 18, 2018 - CRISPR may restore effectiveness of chemotherapies used to treat lung cancer
December 18, 2018 - New app accurately measures and charts progression of skin wounds
December 18, 2018 - Persistent Discrimination ID’d Among Physician Mothers
December 18, 2018 - Cellphone technology developed to detect HIV
December 18, 2018 - A Stanford doctor hits the field with the 49ers — as their airway management physician
December 18, 2018 - The Rise of Anxiety Baking
December 18, 2018 - Just one night of sleep deprivation increases the urge to eat
December 18, 2018 - Study reveals mechanism behind failed remyelination in MS
December 18, 2018 - New genetic testing method increases the precision of biomarker analysis
December 18, 2018 - Simple technique to effectively treat underdiagnosed cause of debilitating chest pain
December 18, 2018 - Barbershop-based medical intervention can successfully lower blood pressure, new data shows
December 18, 2018 - Food labels have caused changes in consumers’ intake and industry’s use of key additives
December 18, 2018 - Sickest children could benefit from split liver transplants
December 18, 2018 - Scientists create patient-specific model to identify most effective treatment for appendix cancer
December 18, 2018 - ‘Little Foot’ endocast reveals a small brain combining ape-like and human-like features
December 18, 2018 - New therapy for childhood blindness shows ‘very promising’ results
December 18, 2018 - Researchers discover promising new compound against Buruli ulcer
December 18, 2018 - Study finds significant use of traditional, complementary and alternative medicines in Sub-Saharan Africa
December 18, 2018 - California Farm Implicated in Outbreak of E. coli Tied to Romaine Lettuce
December 18, 2018 - Mobile health has power to transform HIV/AIDS nursing
December 18, 2018 - Celiac Vaccine in Clinical Trials at Columbia
December 18, 2018 - Research into mental health first aid prompts practical guidance and resources for workplace
December 18, 2018 - Researcher conducts study to investigate peripheral blood markers of Alzheimer’s disease
December 18, 2018 - Researchers identify link between mucus in the small airways and pulmonary fibrosis
December 18, 2018 - EU Commission’s Health Policy Platform to host EKHA program on transplantation
December 18, 2018 - Survivors of childhood Hodgkin lymphoma have high risk of developing solid tumors
December 18, 2018 - Small changes to cafeteria design can get kids to eat healthier, new assessment tool finds
December 18, 2018 - From Machines to Cyclic Compounds
December 18, 2018 - New study reveals best assessment tools to establish delirium severity
December 18, 2018 - Rice University scientists develop synthetic protein switches to control electron flow
December 18, 2018 - Home-based pulmonary function monitoring for teens with Duchenne muscular dystrophy
December 18, 2018 - Researchers identify potential target for new breast cancer treatments
December 18, 2018 - National Biofilms Innovation Centre award grant to Neem Biotech for novel anti-biofilm drug development
December 18, 2018 - Artificial intelligence and the future of medicine
December 18, 2018 - Montana State doctoral student receives grant for her work to improve neuroscience tool
December 18, 2018 - Early postpartum initiation of opioids associated with persistent use
December 18, 2018 - Russian scientists identify molecular ‘switch’ that could be target for treatment of allergic asthma
December 18, 2018 - Surgeons make more mistakes in the operating room during stressful moments, shows study
December 18, 2018 - Immune cells explode themselves to inform about the danger of invading bacteria
December 18, 2018 - Malnutrition in children with Crohn’s disease linked with increased risk of surgical complications
December 18, 2018 - FDA Approves Motegrity (prucalopride) for Adults with Chronic Idiopathic Constipation (CIC)
December 18, 2018 - The long and short of CDK12
December 18, 2018 - Hologic’s Cynosure division introduces TempSure Surgical RF technology in North America
December 18, 2018 - CMR Surgical partners with Nicholson Center to launch U.S.-based training program for Versius
December 18, 2018 - Findings reinforce guidelines for cautious use of antipsychotics in younger populations
December 18, 2018 - Study finds new strains of hepatitis C virus in sub-Saharan Africa
December 18, 2018 - New battery-free, implantable device aids weight loss
December 18, 2018 - Parental alcohol use disorder associated with offspring marital outcomes
December 18, 2018 - Novel Breast Imaging Technique Might Cut Unnecessary Biopsies
December 18, 2018 - What can a snowflake teach us about how cancer spreads in the body?
December 18, 2018 - Management of nausea and vomiting in pregnancy costs the NHS more than previously thought
December 18, 2018 - Green leafy vegetables may reduce risk of developing liver steatosis
December 18, 2018 - Veganism linked to nutrient deficiencies and malnutrition if not planned correctly
December 18, 2018 - Coming Soon: A Tiny Robot You Swallow to Help You Stay Healthy
December 18, 2018 - Modified malaria drug proven effective at inhibiting Ebola
December 18, 2018 - Study finds epigenetic differences in the brains of individuals with schizophrenia
December 18, 2018 - Fitness instructors’ motivational comments influence women’s body satisfaction
December 18, 2018 - Study focuses on modification of lipid nanoparticles for successful brain cell targeting
December 18, 2018 - New gut bacteria may be effective against obesity, metabolic and mental disorders
December 18, 2018 - New two-in-one powder aerosol to upgrade fight against deadly superbugs in lungs
December 18, 2018 - Biofilms feed with swirling flows
New research finds that MHC-II molecules have more influence on tumors than MHC-I

New research finds that MHC-II molecules have more influence on tumors than MHC-I

image_pdfDownload PDFimage_print

Cancer immunotherapy — efforts to boost a patient’s own immune system, allowing it to better fight cancer cells on its own — has shown great promise for some previously intractable cancers. Yet immunotherapy doesn’t work for everyone, for reasons that aren’t always clear. Most research and new therapies in this field have been focused on CD8+ T cells, a type of immune cell that recognizes and destroys other cells that display cancer antigens (mutated proteins that help give rise to tumors). Meanwhile, another type of immune cell, CD4+ T cells, and the molecular signals they recognize have received less attention.

Using a bioinformatics approach, University of California San Diego School of Medicine researchers found that CD4+ T cell’s binding partner, a molecule called MHC-II, may have even more influence on emerging tumors than MHC-I, the better known partner of CD8+ T cells.

The finding, published September 20 in Cell, may help researchers improve cancer immunotherapies and predict which patients will respond best.

“The more we know about the ability of a person’s immune system to clear cancer cells before they take hold, and the more we can combine that with other information about their inherited risk factors or environmental exposures, the better we may get at predicting a person’s cancer susceptibility,” said senior author Hannah Carter, PhD, assistant professor of medicine at UC San Diego School of Medicine. Carter led the study with first author Rachel Marty, a graduate student in her lab.

Know your MHCs

Carter and Marty’s study centers on the Major Histocompatibility Complex (MHC), a family of molecules displayed on the surface of most cells in the body. MHCs hold out antigens — bits of just about everything from inside the cells — and display them to T cells, immune system surveyors that are constantly checking for infected or damaged cells. If T cells spot MHC molecules with “self” antigens, they leave the cell alone. But if they spot foreign antigens, like those from bacteria or viruses, or mutated self-antigens, they kill the cell before the damage spreads.

In a previous Cell study, Carter, Marty and team found clear associations between a person’s MHC-I genetic makeup and the genes mutated in that person’s cancer. That makes sense, Carter said, since cancer antigens that are presented by MHC-I would lead to early elimination of those cancer cells by T cells. From the opposite point of view, if a person’s MHC-I molecule does not recognize and display a cancer antigen, that particular abnormality is more likely to show up in that person’s tumor. This played out clinically, too — the researchers found that the fewer the cancer antigens a person’s MHC-I can recognize, the earlier in life they’re likely to get cancer.

Carter said that it’s possible this information could someday be used to predict the type of cancer a person might get, how it might behave and how it might best be treated, all before the tumor even gets started.

But MHC-I doesn’t tell the whole story about the ability of a person’s immune system to respond to tumors. Humans also have a related molecule called MHC-II. MHC-I is displayed on the surface of every cell, and thus any cell with the potential to become cancerous. MHC-II, on the other hand, is only displayed by professional immune cells, such as macrophages. MHC-II is also a more complex molecule, and it can bind a larger range of antigens than MHC-I. Both molecules play an important role in keeping would-be tumors in check — while cancer cell precursors might be able to evade detection by one, they’re less likely to escape both.

New findings

Curious about the underappreciated member of the MHC family, Carter’s team focused on MHC-II in their latest study. Similar to their MHC-I study, they applied computational biology methods to data available from The Cancer Genome Atlas (TCGA), the National Institutes of Health’s database of genomic information from thousands of different human tumors. They scored 5,942 patient tumors based on the ability of their MHC-II molecules to present 1,018 cancer antigens for inspection by their CD4+ T cells.

The researchers found that an antigen that is well recognized by a person’s MHC-II is less likely to show up in his or her tumor than a mutation overlooked by MHC-II. This was even more true for MHC-II than MHC-I.

However, Carter and team were surprised to find that, unlike MHC-I, MHC-II’s ability to recognize antigens had no correlation with the age at which a person was diagnosed with cancer.

“Imagine there are 100 mutated antigens that can cause cancer,” Carter said. “If a person’s MHC-I can only present 20 of those antigens, they would have less coverage than someone who can present 80. When people can’t present a lot of mutations, they tend to get cancer at an earlier age. That’s true for MHC-I, but we couldn’t find that same correlation for MHC-II, at least not in this early analysis.”

Looking ahead

MHC-II is more complex than MHC-I, and the tools for studying MHC-II are not yet as sophisticated, Carter said. But as the field advances, she hopes to see researchers and clinicians take both MHC-I and MHC-II data into account when developing and personalizing cancer immunotherapies. She believes this information could help determine why some people respond to immunotherapy and others don’t. What’s more, she hopes doctors might someday be able to use MHC-I and -II readouts to predict a patient’s response before they are given immunotherapy, sparing non-responding patients from the potential side effects of ineffective therapies.

“Bringing MHC into the big picture of cancer through genomic analysis is a powerful new way to integrate the master regulator of immunity into a better understanding of cancer evolution and its dynamic interplay with the immune system,” said study co-author Maurizio Zanetti, MD, professor of medicine at UC San Diego School of Medicine and head of the Laboratory of Immunology at Moores Cancer Center. “This may represent a step forward in our ability to select the best form of immunotherapy for individual patients and likewise help better predict response to immunotherapy. I see this work as a major step to bridge cancer genomics and cancer immunity.”

Source:

https://health.ucsd.edu/news/releases/Pages/2018-09-20-cancer-immunotherapy-might-benefit-from-previously-overlooked-immune-players.aspx

Tagged with:

About author

Related Articles