Adoptive Cell Transfer of Lymphocyte Antigen 6A Knockout (Ly-6A-/-) T cells suppresses melanoma tumor growth and enhances the endogenous immune response in a wild-type murine model 3150

Abstract Description Ly-6A is a GPI-anchored protein expressed on T cells that disrupts TCR signaling and inhibits T cell activation. The Ly-6A-/- T cells were adoptively transferred (ACT) into wild-type mice challenged with B16-F10 melanoma and demonstrated a 96% decrease in average tumor load at 14 days post-tumor induction (Ly6-A -/- ACT n = 6, 0.01cm3, WT ACT n = 6 0.30cm3) and a 25% decrease at day 21 (Ly6a KO ACT n = 6, 0.65cm3, WT ACT n = 6 0.87cm3). The CD25 expression on endogenous immune cell populations within the draining lymph node of the Ly6a KO ACT group was 242% higher than that of the WT ACT group (Ly6a KO ACT n = 6 3.06%, WT ACT n = 5 1.26%). ACT injections were formulated from isolated peripheral lymph node T cells and given intravenously into the lateral tail vein at 10 x106 T cells per injection. CD4+ and CD8+ cell distribution within all ACT injections showed no significant difference (% CD4+/CD8+, Ly-6A KO ACT 57/42, WT ACT 58/41). B16-F10 tumor growth was initiated 24 hours post ACT through subcutaneous injection of 2 x 105 cells in 100 µL of B16-F10 cells into the left flank. Electronic calipers measured tumor growth. Tissues were harvested when tumor growth reached 1 cm3, and cell populations were analyzed by FACS analysis. These results demonstrate that Ly-6A KO T cells effectively suppress tumor growth and promote endogenous immune responses. These findings identify Ly-6A KO T cells as a potential novel cell population for cell-based cancer immunotherapies. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)