Dr Jain on the Impact of CD39+ T Cells on CAR T-Cell Phenotype

Michael Jain, MD, associate member, ICE-T Medical Director, Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, discusses the importance of evaluating the impact of lymphoma-associated CD39-positive T cells on CAR T-cell phenotypes.

Autologous CAR T-cell therapy is an established standard of care for patients with relapsed or refractory large B cell lymphoma (LBCL). However, the patient-specific factors that influence the quality of CAR T-cell products remain unclear, Jain begins. Previous research emphasized the importance of starting with high-quality T-cells for optimal outcomes when treating a patient with CAR T-cell therapy, he explains, noting that patients with cancer may have compromised T-cell quality due to factors like recent chemotherapy.

In a retrospective single-center cohort study of patients withLBCL receiving CD19 CAR T-cell therapy, researchers explored the impact of increased CD39-positive T-cells expression in the starting leukapheresis material on CAR T-cell product characteristics. CD39 is an ectonucleosidase specifically upregulated on CD4-positive regulatory T-cells and exhausted CD8-positive T-cells in cancer. It is known to play a role in nucleoside conversion and apoptosis susceptibility. CD39 positive T-cells are often found in patients with high lymphoma tumor burden and are associated with poor CAR T-cell quality and adverse outcomes in patients.

Results from the investigation showed that increased numbers of CD39-positive T-cells in the leukapheresis material caused manufactured CAR T-cells to display less favorable product characteristics, including higher CD39 expression and fewer memory cells in both paired patient samples and in experiments of in vitro CAR T-cell manufacturing.

However, this effect on T-cell quality was deemed minor, contrary to expectations, Jain states. Instead, tumor characteristics such as size exerted greater influence, he reports. Tumors are known to be immunosuppressive, which is linked to impaired T-cell quality. Jain explains.

The study highlighted the need for future research to discern the specific tumor characteristics leading to poor-quality T-cells, as this aspect could help identify which patients are more likely to achieve long-term remission when undergoing CAR T-cell therapy, Jain concludes.