Effector memory CD8 T cells and central memory CD4 T cells dominate a proliferation deficient T cell population in the primary tumor of breast cancer patients (P2207)

Abstract

Abstract Much of our knowledge on breast cancer derives from research on animal models of the disease. Studies on human breast cancer patient samples offers potential data that is more readily translatable to clinical therapeutics. We found a significant reduction in the proliferative capability of ex vivo T cells from primary tumor tissue compared to those from paired sentinel lymph nodes (SLNs). Central memory T cells have previously been shown to have a higher proliferative capacity than effector memory T cells. We found higher proportions of effector memory cells among tumor infiltrating CD8 T cells as compared to SLN CD8 T cells. Conversely, the CD4 compartment in both tumors and SLNs was dominated by central memory CD4 T cells. We therefore considered that the diminished T cell proliferative capacity may also be explained by a CD4 compartment comprised of anergic or exhausted cells. Further examination of the tumor and SLN CD4 T cells showed only a small population producing IFNγ or IL-17 in response to TCR stimulation, which may support this possibility. We hypothesize that these observations are symptoms of an inefficient T cell response to tumor cells in breast cancer patients. Diminished T cell proliferative capacity in the tumor may be explained by the predominant effector memory status of TIL CD8s and reinforced by the presence of anergic CD4 T cells. Future characterization of these T cells will be useful to design treatments that enhance their anti-tumor ability.