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Researchers at Moffitt Cancer Center have found that tapping into the body's own immune system and activating a type of immune cell known as B cells, could be the key to boosting the effectiveness of tumor-infiltrating lymphocyte, or TIL therapy. Results of their study were published in the Journal for Immunotherapy of Cancer . TIL therapy starts with doctors removing tumors from the patient.
These tumors are sent to a lab, where they are dissected to collect immune cells that have infiltrated the tumor, known as tumor-infiltrating lymphocytes (TILs). These TILs are then grown in large quantities and reinfused into the patient's body to seek out and attack cancer cells. While it's already FDA-approved for melanoma, new Moffitt research shows that a simple tweak in the lab could make it work even better for more patients.
The key is a natural immune protein called CD40L. "We discovered that by adding CD40L to the immune cells in the lab, we could dramatically improve the number and quality of cancer-fighting T cells we're able to grow," said Daniel Abate-Daga, Ph.D.
, scientific director of the Cell Therapies Core at Moffitt and lead author of the study. "It's like flipping a switch that helps these cells become stronger and healthier." Results of the study showed that in more challenging specimens, TIL cultures grew successfully in 67% of samples when CD40L was used, compared to 33% without it.
The approach also shaved up to one week off the manufacturing time, potentially getting the cellular immunotherapy to patients sooner. Finally, the enhanced cells were more "stem-like," a trait linked to longer-lasting cancer-fighting capabilities. "TIL therapy is one of the most promising treatments we have for solid tumors ," said Abate-Daga.
"This discovery could help more patients benefit and do so more quickly." Moffitt is currently leading a clinical trial to test this approach in patients with non-small cell lung cancer . Researchers hope CD40L-enhanced TILs will become a next-generation standard in TIL therapy.
More information: Renata Ariza Marques Rossetti et al, CD40L stimulates tumor-infiltrating B-cells and improves ex vivo TIL expansion, Journal for ImmunoTherapy of Cancer (2025). DOI: 10.1136/jitc-2024-011066.
