Breaking News
April 18, 2019 - Diabetic drug shows potential to be repurposed as heart disease treatment for non-diabetic patients
April 18, 2019 - New estimation method assesses natural variations in sex ratio at birth
April 18, 2019 - UTA scientist receives $1.17 million grant for cancer research
April 18, 2019 - Coagulation factor VIIa prevents bleeds in hemophilia animal models
April 18, 2019 - Researchers identify risk factors for severe infection after knee replacement
April 18, 2019 - Mass drug administration can offer community-level protection against malaria
April 18, 2019 - FDA’s added sugar label could have substantial health and cost-saving benefits
April 18, 2019 - Researchers identify cause of inherited metabolic disorder
April 18, 2019 - Single strip of white paint not sufficient to protect people who ride bikes
April 18, 2019 - Partner status influences link between sexual problems and self-efficacy in breast cancer survivors
April 18, 2019 - Colorectal Neoplasia Risk Up for Hodgkin Lymphoma Survivors
April 18, 2019 - Rigid spine muscular dystrophy – Genetics Home Reference
April 18, 2019 - Simple bile acid blood test could tell risk of stillbirth
April 18, 2019 - Center for Experimental Therapeutics aims to enable all steps of drug development | News Center
April 18, 2019 - Falling for telephone scams could be an early sign of dementia
April 18, 2019 - Researchers annotate key neuronal proteins in lamprey genome
April 18, 2019 - Study uncovers new biomarker for personalized cancer treatments
April 18, 2019 - Scientists enter research collaboration to find a cure for cancer
April 18, 2019 - Study to compare benefits of tai chi and mindfulness meditation on MS symptoms
April 18, 2019 - Gestational diabetes during pregnancy may increase risk of type 1 diabetes in children
April 18, 2019 - Is a New Remedy for Body Odor on the Horizon?
April 18, 2019 - Orthostatic hypotension – Genetics Home Reference
April 18, 2019 - Healing the heartbreak of stillbirth and newborn death
April 18, 2019 - Conference to highlight advances in human immune monitoring, bioinformatics | News Center
April 18, 2019 - Bacteria use viruses for self-recognition, study reveals
April 18, 2019 - New adhesive patch could help reduce post-heart attack muscle damage
April 18, 2019 - Researchers analyze the effects of dark play in a serious video game
April 18, 2019 - Filial cannibalism and offspring abandonment may be forms of parental care
April 18, 2019 - Two proteins act in concert to maintain a healthy heart in mice, shows study
April 18, 2019 - Scientists create a functioning 3D printed heart
April 18, 2019 - Non-invasive vagus nerve stimulation improves disease symptoms in patients with rheumatoid arthritis
April 18, 2019 - Majority of men struggle to understand diagnosis and treatment of prostate cancer
April 18, 2019 - Researchers create new small molecules that may combat equine encephalitis viruses
April 18, 2019 - Animal-assisted therapy improves social behavior in patients with brain injuries
April 18, 2019 - Some viruses help protect harmful bacteria in CF patients | News Center
April 18, 2019 - Outpatient healthcare providers inappropriately prescribe antibiotics to 40% of patients
April 18, 2019 - Men who have a resting heart rate of 75 bpm are twice as likely to die early
April 18, 2019 - Novel serum biomarkers to detect NAFLD-related fibrosis
April 18, 2019 - New study delves deeper into individual genomic differences than ever before
April 18, 2019 - Gilead and Galapagos Announce Filgotinib Meets Primary Endpoint in the Phase 3 FINCH 3 Study in Methotrexate-Naïve Rheumatoid Arthritis Patients
April 18, 2019 - Emotional mirror neurons found in rats
April 18, 2019 - Sylvia Plevritis appointed chair of biomedical data science | News Center
April 18, 2019 - Yeast strain provides manufacturing boost to low-calorie sweetener derived from lactose
April 18, 2019 - One in five children and youth suffer from a mental disorder
April 18, 2019 - Improper inhaler use common in children with asthma
April 18, 2019 - C-Path and CDISC release global Therapeutic Area Standard for HIV research
April 18, 2019 - Integrating AI to analyze imaging data allows early recognition of heart disease
April 18, 2019 - Low-cost, high-speed algorithm may allow animal-free chemical toxicity testing
April 18, 2019 - HPV-negative cervical cancers are more aggressive with worse prognosis
April 18, 2019 - AI detects prostate cancer with same level of accuracy as experienced radiologists
April 18, 2019 - Study resolves sex differences in psychiatric illness risk
April 18, 2019 - Novartis Announces FDA Filing Acceptance and Priority Review of Brolucizumab (RTH258) for Patients with Wet AMD
April 18, 2019 - Cocktail of common antibiotics can fight resistant E. coli
April 18, 2019 - Persis Drell to give keynote address at medical school diploma ceremony | News Center
April 18, 2019 - EpicTogether: Remembering Our Why
April 18, 2019 - Study identifies novel loci contributing to asthma susceptibility in adults
April 18, 2019 - Gut bacteria and pregnancy
April 18, 2019 - New study finds that screening could help prevent rare types of cervical cancer
April 17, 2019 - Spatial orgnization of the genome can be altered using small molecules
April 17, 2019 - AEDs Tied to Higher Pneumonia Risk in Alzheimer Patients
April 17, 2019 - Telemedicine tied to more antibiotics for kids, study finds
April 17, 2019 - Two medical students awarded 2019 Soros Fellowships for New Americans | News Center
April 17, 2019 - Sociologist Constance A. Nathanson Awarded Guggenheim Fellowship
April 17, 2019 - Empathy and hormones could account for aggressive behavior in children, shows study
April 17, 2019 - Researchers develop oral appliance to help sufferers of sleep apnea
April 17, 2019 - Neuronal transport factor detects its target transcripts in more complex manner than previously thought
April 17, 2019 - New drug-delivery system senses high oxidant levels, responds to body chemistry and environment
April 17, 2019 - Health Tip: Horseback Trail Riding Safety
April 17, 2019 - Scientists outline the promises and pitfalls of machine learning in medicine
April 17, 2019 - $12 million grant renewal for flu vaccine research | News Center
April 17, 2019 - Lisa Kachnic, MD, Joins Columbia University as Chair of Radiation Oncology
April 17, 2019 - New study sheds light on how extreme temperature hampers spermatogenesis in insects
April 17, 2019 - Study tests high-tech, non-pharmaceutical way to address ADHD and distractibility
April 17, 2019 - New EZ-2 evaporator for clinical biochemistry sample preparation
April 17, 2019 - Fat shaming celebrities may make women more judgemental about being overweight
April 17, 2019 - Magic mouthwash effectively reduces mouth sore pain caused by radiation therapy
April 17, 2019 - CBD could help slip medications into the brain
April 17, 2019 - Scientists characterize 2017 pneumonic plague outbreak in Madagascar
April 17, 2019 - Human iPSC-derived MSCs from aged individuals acquire a rejuvenation signature
April 17, 2019 - Gun Research Is Suddenly Hot
GARP protein can be a potential target for immunotherapy against colorectal cancer

GARP protein can be a potential target for immunotherapy against colorectal cancer

image_pdfDownload PDFimage_print

Colorectal cancer is the third leading cause of cancer-related deaths in both men and women. Despite significant advances in therapies for this particular cancer, the five-year survival rate is 12 percent, according to the American Cancer Society.

Immunotherapies have emerged as a promising treatment for many cancers and are effective against melanoma, lung cancer, and renal cell carcinoma. These immunotherapies include checkpoint therapies such as PD-1 inhibitors, which help activate the immune system against the cancer.

Despite the promise these immunotherapies hold, clinical trials involving PD-1 inhibitors have been disappointing against colorectal cancer. Further, only a subset of colorectal cancer patients with certain mutations seem to respond well to anti-PD-1 therapy.

In an article published in the March issue of Cancer Research, Zihai Li, M.D., Ph.D., and his team at the Medical University of South Carolina (MUSC) report a potential new target for immunotherapy directed against colorectal cancer.

Like PD-1, GARP is a protein expressed on the surface of our immune cells. Li and his team hope that targeting this protein could be a potential therapy for colorectal cancer patients who do not respond to other immunotherapies.

“In terms of cancer therapy, the immune system has so many buttons you can push,” says Li. “PD-1 checkpoint therapy is an example of that. Researchers are constantly looking for more buttons to push, and I think that GARP could be one of those buttons.”

Li is chair of the Department of Microbiology and Immunology at MUSC and co-leads the cancer immunology research program at MUSC Hollings Cancer Center.

An important balance exists within the immune system. While we need our immune system to protect us against diseases like cancer, we also need regulatory mechanisms to keep it from attacking our body. Collectively, these are known as tolerance.

Cancer takes advantage of tolerance mechanisms to hide from our immune system. T cells are a type of immune cell that can target and kill cancer cells. However, they can come in many different flavors. One flavor, called a regulatory T (Treg) cell, makes sure we maintain tolerance to our own cells. Cancer cells can increase the presence of Treg cells in order to avoid being killed off by other types of T cells.

Li and his lab have always been interested in how Tregs can be regulated both in terms of tolerance and in disease states like cancer. The research team led by Li found that disrupting GARP, a cell surface receptor on T regulatory cells, decreases tolerance, reduces colon cancer development, and inhibits migration of Treg cells to the gut in a preclinical model.

“Fundamentally we shed some light on basic T regulatory cell biology,” explains Li. “We found that GARP, specifically that on T regulatory cells, is important for immune tolerance. It also seems to be involved in immune evasion by cancers in the gut.”

The MUSC team showed that, in a mouse model of colitis, genetic deletion of GARP on Treg cells prevented the immune system from maintaining optimal tolerance in the gut. Without GARP, the Treg cells could no longer efficiently suppress the immune system and fewer of them traveled to the gut. Further, the team showed that deleting GARP on Treg cells in a mouse model of colon cancer diminished tumors by half compared with mice with intact GARP.

“In our preclinical cancer model, mice with no GARP on their Treg cells had a better outcome, and more T cells infiltrated the tumor,” says Li. “Interestingly, this only seems to be the case in the gut. When we induced cancer in other places like the skin, there was no difference between mice with or without GARP on Treg cells.”

Another major player involved in the regulation of Treg cells is TGF-beta. TGF-beta is released by cells and can regulate different parts of the immune system. It is known that GARP is involved in TGF-beta activation. Li’s work indicates that GARP and TGF-beta work together to regulate Treg migration to the gut.

If researchers can figure out how colon cancer cells increase Treg homing to the gut, they could block that homing signal. That would enable the immune system to find and eradicate the cancer.

Li and the research team found CD103, a cell surface protein, to be that homing signal.

“When GARP is expressed on the surface of Treg cells, it can grab TGF-beta that’s secreted from other cells,” explains Li. “This causes an upregulation in CD103 expression, which acts like a zip code to the gut for Treg cells.”

Ultimately, the MUSC’s team is the first to show the role that GARP plays in regulating the activity of Treg cells in the colon. Their next steps will be to characterize the presence of GARP on Treg cells in human colon cancer, as GARP can be therapeutically targeted.

“It turns out that colon cancer patients have high levels of TGF-beta, which upregulates Treg cells”, says Li. “This may be one of the reasons why they don’t respond to PD-1 therapy. However, these could be the patients that anti-GARP therapy could work really well on.”

Tagged with:

About author

Related Articles