Featured Post from ChristianaCare

ChristianaCare Scientists Show for the First Time That Tumor Cells Can Manipulate the Body’s Natural Antibody Response to Triple Negative Breast Cancer

Apr 26, 2022

4 min

Findings point to potential new therapeutic targets for this highly aggressive, drug-resistant breast cancer subtype


In breakthrough research at ChristianaCare’s Helen F. Graham Cancer Center & Research Institute, scientists have discovered that a protein secreted by tumor cells can switch off the body’s natural defenses against triple negative breast cancer (TNBC).


The study, led by Jennifer Sims-Mourtada, Ph.D., lead research scientist at the Cawley Center for Translational Cancer Research (CTCR), at the Graham Cancer Center, is reported in The Journal of Translational Medicine, available online.


“What we found is that TNBC tumor cells can effectively shut down the body’s defense systems against the tumor by secreting a type of protein called IL-10,” Dr. Sims-Mourtada said.


“The presence of this immune system protein forces the antibodies that would normally be created to attack the tumor to become non-reactive and not do what they are supposed to do.”


The study was initiated in partnership with The Wistar Institute of Philadelphia, Pennsylvania, in collaboration with the late Raj “Shyam” Somasundaram, Ph.D., a cell biologist at the Melanoma Research Center.


“Dr. Sims-Mourtada and her team have brought us tantalizingly close to understanding what drives the aggressive nature of triple negative breast cancer, a treatment-starved disease that disproportionately affects Delaware women,” said Nicholas J. Petrelli, M.D., Bank of America endowed medical director of the Helen F. Graham Cancer Center & Research Institute.


“Their work underscores our belief that scientific collaborations such as this one between our Cawley CTCR clinicians and Wistar scientists can smooth the way for new findings to become effective therapies, especially for hard-to-treat and aggressive forms of cancer like TNBC.”


Understanding the mechanism behind TNBC

Delaware ranks highest in the nation for incidence of triple negative breast cancer. TNBC is an aggressive form that affects Black women at twice the rate of white women with poorer outcomes. Patients have higher rates of early recurrence than other breast cancer subtypes, particularly in the first five years after diagnosis. Currently there is no targeted therapy for TNBC.


“One of our missions within the Cawley CTCR is to understand the mechanisms behind TNBC and find a treatment for it,” Dr. Sims-Mourtada said. “Our study sheds new light on what is prompting the body’s immune response to the cancer cells and offers clues to potential new therapeutic targets.”


Normally it is the job of the B cells to regulate the immune response against foreign invaders like cancer. Among other jobs, they control inflammation at the site of an attack by releasing proteins including IL-10 to signal the defender cells to stand down.


“Previously it was thought that the immune cells were the ones to express IL-10 to regulate themselves,” Dr. Sims-Mourtada said. “But our study shows that the tumor cells also release this protein, which means they are driving how the immune system behaves.”


Within the tumor microenvironment, IgG4 is one of four antibody subclasses expressed and secreted by B cells. Whereas another type of antibody would urge the immune system to press on with the attack, activation of IgG4 signals the job is done.


TNBC and activation of IgG4

“Our findings support that TNBC may create a tumor environment that supports activation of IgG4, and messaging from IL10 is triggering the switch,” Dr. Sims-Mourtada said.


As previously reported with other cancers, such as melanoma, this study confirms that the presence of IgG4-positive B cells within the tumor associates with advanced disease increased recurrence and poor overall breast cancer survival. It is also possible that IL-10 expression by tumor cells may also be a cause of poor outcomes in TNBC, and this may be independent of IgG4+ B cells.


“At this point, we don’t know what causes tumor cells to start secreting IL-10, but we know that B cell-tumor cell interactions are involved,” Dr. Sims-Mourtada said.


“We still have to look at what is really going on in the B cell population to determine which subtypes of B cells are affected by this tumor crosstalk and why some forms of TNBC express IL-10 (the ones with poor outcomes) and others do not.


“We think that the presence or absence of other immune cells in the microenvironment may affect how B cells interact with tumor cells to drive IL-10 expression,” she said.


Resources for the study, including blood and tissue samples from consenting patients, were obtained through the Graham Cancer Center’s Tissue Procurement program. Interestingly, in a small subset of samples, the researchers found that IL-10 expression was significantly higher in Black patients than non-Hispanic white patients. These findings need to be confirmed in a larger more diverse population with different TNBC subtypes.


Understanding tumor-infiltrating B cells

“Our growing understanding of the contribution of IgG4+ cells to the immune microenvironment of TNBC and what drives IL-10 expression may reveal ways in which tumor-infiltrating B cells can contribute to tumor growth and provide new targets to increase the immune response to TNBC,” Dr. Sims-Mourtada said.


As partners for more than a decade, Graham Cancer Center research clinicians and Wistar scientists collaborate across disciplines to translate cancer research into more effective therapies for patients everywhere. In addition to providing high-quality, viable tissue samples for Wistar research studies, Graham Cancer Center clinicians actively participate in concept development, sharing their unique understanding of the everyday patient experience.


You might also like...

Check out some other posts from ChristianaCare

3 min

New Outpatient Cardiology Practice at Wilmington Hospital Expands Access to Life-Saving Care for Patients with Peripheral Artery Disease

With the opening of a new cardiology practice at its Wilmington campus, ChristianaCare is bringing life-saving treatment for peripheral artery disease (PAD) closer to home for people who live in and around the city of Wilmington. Peripheral artery disease happens when plaque builds up in the arteries and limits blood flow to the legs. This can cause pain, cramping and difficulty walking. If left untreated, it can lead to serious problems like limb loss, heart attack or stroke. “We’re on a mission to improve the heart and vascular health of our community, and one of the key ways we do that is to identify where people need access to care and ensure that it’s convenient, high-quality and accessible. ChristianaCare’s expansion of cardiology services to the Wilmington campus has made it easier for patients in Wilmington and the surrounding community to receive excellent heart and vascular care,” said Kirk Garratt, M.D., MSc, medical director of the Center for Heart and Vascular Health. “Importantly, it’s part of a multi-disciplinary effort to bring a focus on PAD that includes vascular surgery and interventional radiology. We’re expanding those services in the Wilmington community, too.” In Delaware, an estimated 45,000 to 50,000 people are living with PAD. The condition is more common among older adults and those with diabetes, high blood pressure or a history of smoking, all of which are widespread in the state. Because symptoms can be subtle, many people may not know they have it. That’s why awareness and early diagnosis are so important. Anyone who experiences leg pain, numbness or slow-healing sores should talk with their doctor. A simple test can measure blood flow, and with the right treatment or lifestyle changes, people can ease symptoms and lower their risk of serious complications. The new practice, located in the Gateway Building at Wilmington Hospital, 501 West 14th Street, 4th Floor, offers convenient access to diagnosis and treatment in the heart of the city. The practice is open on Wednesdays from 8 a.m. to 12 p.m., and hours will be adjusted based on patient demand. Meet the Cardiologist: Dr. Vikashsingh Rambhujun Board-certified interventional cardiologist Vikashsingh Rambhujun, MBBS, has cared for ChristianaCare patients for more than a decade and now sees patients at the Wilmington practice. Rambhujun earned his medical degree from SSR Medical College in Mauritius. He completed his residency in internal medicine at the NYU Grossman Long Island School in New York and did his fellowship in cardiovascular medicine and interventional cardiology at ChristianaCare. Rambhujun also spent a year doing interventional cardiology and endovascular medicine and interventions at Yale University Hospital in New Haven, Connecticut. His research has been published widely in medical journals. Rambhujun aims to help patients manage PAD before it becomes advanced. When appropriate, he can perform minimally invasive catheter-based procedures to open blockages in the arteries. “We have new patients with blockages that haven’t progressed to the point that they need a procedure, which is where we want to catch them,” Rambhujun said. “We can manage their cholesterol, blood pressure and other risk factors to prevent disease from progressing.” When Rambhujun began practicing in Wilmington, he made it a priority to speak at local community meetings, raising awareness about the warning signs of heart and vascular disease. His message is simple but urgent: don’t wait; seek treatment early. “We’re trying to help people keep their toes and feet,” he said. “When we treat blockages from peripheral artery disease, the difference can be dramatic,” he said. “Patients who once struggled to walk even a short distance because of pain can leave the hospital able to move freely again. Helping someone reclaim their basic freedoms to walk, stay active and enjoy life is incredibly rewarding.”

2 min

ChristianaCare Breaks Ground on New Middletown Health Center

ChristianaCare today broke ground on its new Health Center at Middletown, marking a major milestone in bringing expanded, affordable and exceptional care to families in southern New Castle County and northern Kent County. The center is expected to open in spring 2027. The $92.3 million project reflects a deep investment in the health and vitality of the region and is part of ChristianaCare’s larger plan, announced in July, to invest more than $865 million in Delaware over the next three years. The 87,000-square-foot Health Center will rise at 621 Middletown Odessa Road, next to ChristianaCare’s existing freestanding emergency department. Designed as a modern, multidisciplinary hub, the facility will expand access to comprehensive services and create more than 70 new full-time jobs, boosting both community health and the local economy. “Today we take an exciting step forward for Delaware, as part of ChristianaCare’s $865 million investment to expand access and strengthen health across our state,” said Janice E. Nevin, M.D., MPH, President and CEO of ChristianaCare. “This new health center is a promise to Delawareans: that they will have access to exceptional care close to home, delivered with love and excellence. More than a building, it represents our vision for healthier communities, our deep commitment to those we serve, and a future where every neighbor can thrive.” A Holistic, Patient-Centered Experience The ChristianaCare Health Center at Middletown will bring together a wide range of services in one convenient location, including: Primary and specialty care. Women’s health, behavioral health, oncology, cardiovascular care, pediatrics, neurology, imaging, diagnostics and lab testing. Hybrid exam rooms with interactive digital tools that allow family members to join virtually. Calming waiting areas with sensory-sensitive design features, plus friendly floor ambassadors to help patients navigate the building. Healing environments that include walking trails and abundant natural light. “We are designing care around people, not around appointments or buildings,” said Pauline Corso, president of Ambulatory Network Continuity and Growth at ChristianaCare. “From easy parking to advanced care coordination, every detail of this new center is aimed at making health care more welcoming, more connected and more human.” A Community Partnership ChristianaCare has been part of the Middletown community since 2009, when it first acquired the land that is now home to the freestanding emergency department. Last year, that facility provided care for more than 32,000 patient visits. “This groundbreaking is a proud moment for our town,” said Ken Branner, mayor of Middletown. “ChristianaCare has been a trusted partner for many years, and this new facility shows a lasting commitment to our residents. It will bring top-quality care closer to home and create good jobs right here in our community.”

2 min

ChristianaCare’s Center for Virtual Health Earns NCQA Accreditation, Setting a National Standard in Virtual Care

ChristianaCare’s Virtual Primary Care practice at the Center for Virtual Health has earned full accreditation from the National Committee for Quality Assurance (NCQA), placing it among the first health systems in the nation to achieve this distinction. ChristianaCare was one of only 18 organizations invited to participate in NCQA’s inaugural pilot program in 2023 to develop the Virtual Care Accreditation. The recognition affirms ChristianaCare’s leadership role in shaping the future of health care and its commitment to delivering accessible, equitable and patient-centered care through innovative digital platforms. “This accreditation is a powerful validation of our vision to reimagine health care,” said Sarah Schenck, M.D., FACP, executive director of ChristianaCare’s Center for Virtual Health. “We’ve built a model that meets people where they are—at home, at work or on the go—with care that is personal, proactive and powered by love and excellence.” What Accreditation Means for Patients NCQA accreditation underscores that ChristianaCare’s Center for Virtual Health meets rigorous standards for: Clinical quality and safety: clear care protocols, escalation pathways and outcome monitoring. Access and equity: technology, language and disability-inclusive design that extends care to more people. Data privacy and security: strong safeguards to protect personal health information. ChristianaCare’s participation in NCQA’s pilot helped shape the benchmarks now used nationwide. The center delivers comprehensive virtual primary care through a multidisciplinary team that includes physicians, nurses, nurse practitioners, behavioral health specialists, pharmacists and patient digital ambassadors. Virtual Care by the Numbers In 2024, ChristianaCare’s Center for Virtual Health provided more than 7,500 patient visits, reflecting both rapid growth and strong demand for its virtual-first model. Services are offered at no copay to ChristianaCare caregivers and their dependents, while availability continues to expand across Delaware and the region “At ChristianaCare, we believe virtual care isn’t just a convenience, it’s a catalyst for better health outcomes,” said Brad Sandella, D.O., MBA, medical director, Ambulatory Care for the Center for Virtual Health. “This accreditation affirms our commitment to innovation and excellence. We’re proud to be among the pioneers defining what high-quality virtual care looks like in America.” Beginning in 2026, ChristianaCare will expand its Virtual Primary Care practice, giving a broader consumer audience convenient access to primary care. At that time, the service will be covered by most insurance carriers and continue to feature dedicated providers in areas such as behavioral health and neurology. ChristianaCare will also continue working with NCQA and other partners to advance best practices nationwide.

View all posts
Powered by