Cancer biology doctoral student Anna Cole and Winship researcher Chrystal Paulos, PhD, with their colleagues have discovered that Th17 cells and B cells can work together to eliminate solid tumors and prevent recurrence, revealing a powerful new approach to cancer immunotherapy.
Could our own immune cells be the key to stopping cancer from coming back?
Chrystal Paulos, PhD and Anna Cole
A research team at Winship Cancer Institute of Emory University has discovered that two types of immune cells — T helper 17 (Th17) cells and B cells — can work in concert to spark long-lasting protection against solid tumors. Their findings, published in Cancer Cell, show that Th17 immune cells, delivered as a therapy, rely on the body’s own B cells to provide lasting protection against cancer: an unexpected immune partnership that could reshape how cancer is treated.
Led by Chrystal Paulos, PhD, professor of surgery, director of translational research for cutaneous malignancies and co-leader of Winship’s Cancer Immunology Research Program, the study shows that cancer-targeted Th17 cells, generated in the lab, can eliminate tumors, and prevent recurrence— but only when B cells are present to help.
Anna Cole, a PhD student in the Cancer Biology Program at Emory’s Laney Graduate School, led the experiments that uncovered this critical interaction and carried the project through to completion under Paulos’s mentorship.
The power of immune cell teamwork
“This kind of immune cell teamwork — between Th17 cells and B cells — could fundamentally change how we design future cancer therapies,” says Paulos.
“We were surprised to find that the presence of host B cells — not host T cells — was essential for the long-term success of this therapy,” adds Cole. “It changes how we think about immune cell therapy and opens up new possibilities for combining T cells with strategies that harness the antibody-producing side of the immune system.”
Th17 cells are a type of T cell that helps direct immune responses. In this study, researchers used lab-polarized, cancer-specific Th17 cells from donor mice to treat animals with tumors. The therapy not only cleared the tumors but also protected the mice from recurrence — even when they were re-exposed to cancer cells more than 100 days later.
In key experiments, nearly every mouse treated with cancer-fighting Th17 cells remained tumor-free, while untreated animals developed tumors. When B cells were removed or their key immune signals were blocked, the protection disappeared — proving that B cells were essential for the therapy’s success.
One striking result: Serum from Th17-treated mice, rich in tumor-fighting antibodies made by the body’s own B cells, could reduce cancer spread in untreated animals. That finding confirmed, for the first time, that the therapy had triggered a durable, antibody-based immune response — one that depended on B cells.
A collaborative effort
Hannah Knochelmann, MD, PhD
The project was initiated by Hannah Knochelmann, MD, PhD, while a student in the Paulos lab at the Medical University of South Carolina. Her early discoveries on the role of B cells and antibodies shaped the foundation of the study. She is now at Stanford University as a fellow in hematology and oncology.
“Even early on, we suspected B cells might be helping Th17 cells in ways people hadn’t appreciated,” says Knochelmann. “It’s exciting to see that hypothesis evolve into such a robust and clinically relevant finding that might inspire new ways to help people with cancer.”
This breakthrough has already inspired the development of a new human Th17-based tumor-infiltrating lymphocyte (TIL) therapy, now underway in the Paulos lab. Megan Wyatt, a senior translational scientist in the lab, is spearheading the effort to translate this discovery into a TIL-based therapy for patients with cancers that do not respond to immunotherapy. While the current study used lab-polarized, tumor-specific Th17 cells, future versions may involve engineered cells—broadening the potential impact for patients.
The findings also open new therapeutic possibilities for people with weakened B cell function—such as those undergoing chemotherapy or living with immune deficiencies. Ongoing research is focused on identifying the specific cancer targets that trigger this two-cell immune response, paving the way for more personalized and long-lasting cancer immunotherapies.
Key collaborators included Gregory Lesinski, PhD, MPH, professor of hematology and medical oncology, and Jeremy Boss, PhD, professor of microbiology and immunology, both at Emory University School of Medicine, who contributed to immunologic analysis and interpretation.
Funding for this research was provided by the National Cancer Institute (R01CA175061, R01CA208514, R01CA275199, R50CA233168, F30CA243307, F31CA281258, F30CA291027, T32CA272392), the Melanoma Research Foundation, the V Foundation for Cancer Research, the ARCS Foundation, Emory University and Winship Cancer Institute. Shared resources supported by Winship Cancer Institute (P30CA138292) and the Medical University of South Carolina also contributed to the study. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.