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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.


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Through the years, ChristianaCare ACT team members have seen their projects live on both as permanent changes throughout the health system and, more personally, in their professional growth. “I was able to enhance my creativity, organizational and problem-solving skills,” said Starr Lumpkin, a staff assistant who was on the “Hush” team. “This was a pivotal journey for me.” ChristianaCare is growing its program to develop a pipeline for the next generation of health professionals, said Safety and Quality Education Specialist Claire Rudolph, MSM, CPHQ. “We have a varied group of learners and facilitators who are making an impact on health care quality, cost and safety.” Dylan Norris was the first participant from a new partnership with the University of Delaware for pre-med students to get quality improvement experience. “I have learned so much about what goes into a quality improvement project. Buy-in from the stakeholders is key in implementing any new project successfully,” she said. “I have also learned about the importance of the initial research that goes into creating a new project and how much pre-planning goes into it.” Closing the event, Clinical Effectiveness Officer Christian Coletti, M.D., MHCDS, FACEP, FACP, called on the ACT graduates to use their newfound “superpowers” — “vision, seeing the future, catching something before it breaks. “It’s not a glitch in the matrix,” he said. “You are the most important people at the bedside – hearing the alarms going off or the stretchers piling up. Work to identify problems and move toward solutions in your own microenvironments. Pass on your powers with reckless abandon.”

1 min

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Statement by Kirk Garratt, M.D., Medical Director of ChristianaCare's Center for Heart & Vascular Health "A new study is challenging the current approach to preventing heart disease by showing that combining ezetimibe (Zetia) with statins could be a highly effective treatment for all high-risk patients, not just those who can’t tolerate higher doses of statins. Ezetimibe works by blocking the absorption of dietary fats before they reach the liver, while statins block the conversion of these fats into bad cholesterol. Clinical studies have already shown that combining moderate doses of statins with ezetimibe works as well as high doses of statins alone. This new research, which used a sophisticated method to combine results from many studies, demonstrates the potential of using this combination more routinely. The impact could be significant—potentially avoiding thousands of heart attacks and saving many lives each year. Ezetimibe has minimal side effects and is available in generic form, offering a treatment option with few barriers to widespread use. However, patients should speak with their doctor to discuss whether this combination is right for them." Learn more:

3 min

Four-Peat! ChristianaCare Achieves Magnet® — the Top Recognition for Nursing Excellence — for the Fourth Time

Hundreds of nurses and their colleagues at ChristianaCare gathered in a conference room at Christiana Hospital and listened through a livestream across the organization’s campuses and practices for an announcement they’ve been anticipating for many months. “For your commitment to nursing excellence and quality care, we are thrilled to recognize ChristianaCare with its fourth consecutive Magnet designation,” said David Marshall, JD, DNP, RN, chair of the American Nurses Credentialing Center’s Commission on Magnet Recognition. “This accomplishment is a powerful testament to your dedication to the nurses who practice there, the entire health care team, and — most importantly — the patients you serve.” Shouts erupted, balloons and streamers floated up and, in the happy commotion, there was even a little cowbell. As the only four-time Magnet-designated health care organization in Delaware, ChristianaCare has achieved this global recognition — the highest honor in nursing practice — for continued dedication to excellence and innovation, high-quality patient care and experience, nurse engagement and work culture. “Magnet designation recognizes ChristianaCare nurses are simply the best!” said ChristianaCare President and CEO Janice E. Nevin, M.D., MPH. “A fourth Magnet designation is an incredible achievement and reflects the vital importance and commitment of our nurses as we serve together with love and excellence.” ChristianaCare has more than 3,000 nurses, and they make up the largest segment of ChristianaCare’s workforce. ChristianaCare is the largest nonprofit organization and private employer in the state of Delaware. This most recent designation for ChristianaCare includes Christiana Hospital, Wilmington Hospital, ChristianaCare HomeHealth and Community Care Services, through early 2029. What it means to be Magnet “Our fourth consecutive Magnet designation means that our nurses and all of our caregiver colleagues have upheld the ANCC’s very high standards in patient care since our first recognition in 2010,” said ChristianaCare Chief Nurse Executive Danielle Weber, DNP, RN. “That is a long time to bring your ‘A’ game every day — through 15 years of change, including a pandemic — and to sustain growth in professional practice, innovation and culture. Magnet recognition raises the bar for patient care and inspires every member of our team to achieve excellence every day.” The Magnet Recognition Program — administered by the American Nurses Credentialing Center, the largest and most prominent nurses credentialing organization in the world — identifies health care organizations that provide the very best in nursing care, exceptional nurse engagement and professionalism in nursing practice. The Magnet Recognition Program serves as the gold standard for nursing excellence and provides consumers with the ultimate benchmark for measuring quality of care. The ANCC Magnet Recognition Program® has conferred Magnet status to less than 10% of hospitals and health systems in the United States. There are 621 Magnet-designated health organizations internationally. ChristianaCare was the first in Delaware to achieve Magnet designation, in 2010. For nurses, Magnet Recognition means education and development through every career stage, which leads to greater autonomy at the bedside. For patients, it means the very best care, delivered by nurses who are supported to be the very best that they can be. While Magnet is a nursing-led initiative, the designation reflects the work of caregivers across the organization. Magnet redesignation itself is a rigorous process. Health care organizations must reapply for Magnet status every four years and demonstrate adherence to the Magnet concepts for nursing excellence and engagement and measurable improvements in patient care and quality. The ANCC commended ChristianaCare on these exemplars: Advocacy for and acquisition of organizational resources specific to nurses’ well-being. particularly through the Nursing Integrative Care Program. An innovative strategy to address the shortage of certified registered nurse anesthetists in Delaware through a partnership program between ChristianaCare and Wilmington University to launch the state’s first Nurse Anesthesiology program. Outstanding nursing research engagement and growth of the nursing research enterprise especially through the Nursing Research Fellowship in Robotics and Innovation.

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