Document Type
Conference Proceeding
Publication Date
4-16-2019
Abstract
Despite advances in treatment options, cancer remains the second leading cause of death in the United States. Many therapies use immune cells, specifically T cells, for cancer therapy. To enhance tumor recognition by T cells, chimeric antigen receptors consisting of signaling domains fused to receptors that recognize tumor antigens can be created and expressed in T cells. One receptor that is a prospective target for a chimeric antigen receptor is PD1 because the ligands for the PD1 receptor are expressed on many cancer types. Our lab has genetically engineered a chimeric PD1 (chPD1) receptor and has shown that chPD1-expressing T cells kill tumor cells, secrete inflammatory cytokines, reduce tumor burden, and increase survival in multiple tumor types. A current focus of cancer research is the development of combination therapies that enhance anti-tumor efficacy without increasing harmful side effects. Recently, a family of naturally occurring plant compounds called stilbenes have been shown to enhance T cell function. Therefore, we tested if stilbenes enhanced chPD1 T cell function in breast cancer. Addition of resveratrol, a stilbene found in berries, grapes, peanuts, and other plants, decreased proliferation, enhanced tumor cell killing, and increased secretion of proinflammatory cytokines (IFNγ, GM-CSF, TNFα, IL-17, IL-2, and IL-21) from chPD1 T cells. Presence of resveratrol also increased skewing of T cell differentiation to a central memory phenotype through reduction of AKT and mTORc1 signaling, reduced expression of T-bet and BLIMP-1 transcription factors, and increased expression of Bcl-6 and Eomes transcription factors. Hence, combination of resveratrol and chimeric antigen receptor-expressing T cells may enhance anti-tumor immune responses through inhibition of the AKT and mTORc1 pathways and skewing to a long-lived central memory phenotype.
Recommended Citation
Richardson, Elle and Soles, Andrea Leigh, "Enhancing the anti-tumor efficacy of T cells with naturally occurring plant stilbenes" (2019). Undergraduate Publications. 4.
https://digitalcommons.longwood.edu/undergrad_pubs/4
Comments
Faculty Advisor: Amorette Barber