Abstract
Memory T cells are composed of effector, central, and memory stem cells. Previous studies have implicated that both T-bet and Eomes are involved in the generation of effector and central memory CD8 T cells. The exact role of these transcription factors in shaping the memory T cell pool is not well understood, particularly with memory stem T cells. Here, we demonstrate that both T-bet or Eomes are required for elimination of established tumors by adoptively transferred CD8 T cells. We also examined the role of T-bet and Eomes in the generation of tumor-specific memory T cell subsets upon adoptive transfer. We showed that combined T-bet and Eomes deficiency resulted in a severe reduction in the number of effector/central memory T cells but an increase in the percentage of CD62LhighCD44low Sca-1+ T cells which were similar to the phenotype of memory stem T cells. Despite preserving large numbers of phenotypic memory stem T cells, the lack of both of T-bet and Eomes resulted in a profound defect in antitumor memory responses, suggesting T-bet and Eomes are crucial for the antitumor function of these memory T cells. Our study establishes that T-bet and Eomes cooperate to promote the phenotype of effector/central memory CD8 T cell versus that of memory stem like T cells.
Highlights
Tumor growth can elicit type 1 cellular immune responses that limit cancer progression
IL-12 and IFN-c drive T-bet expression, [12,13] and IL-2 promotes Eomes expression. [7,14,15] T-bet and Eomes play an additive role in driving IFN-c production and cytotoxic activities of effector CD8 T cells in vitro. [8,16] T-bet and Eomes coordinately promote T cell migration to inflamed tissues by inducing chemokine receptors. [16,17] In addition, Tbet and Eomes control the expression of CD122 and are required for maintenance of IL-15-dependent memory CD8 T cells. [10,11] High T-bet expression promotes short-lived effector CD8 T cells, whereas low T-bet expression promotes long-lived memory cells
The memory T cells have been typically divided into two main subsets based on the expression of the lymph node homing molecules CD62L and CCR7
Summary
Tumor growth can elicit type 1 cellular immune responses that limit cancer progression. [7,14,15] T-bet and Eomes play an additive role in driving IFN-c production and cytotoxic activities of effector CD8 T cells in vitro. [18], [6,11,19] T-bet and Eomes are important for both function and homeostasis of effector and memory T cells. The role of T-bet and Eomes in the setting of memory T cell responses to tumor antigens is unknown. T-bet and Eomes are known to be involved in both function and homeostasis of effector and memory T cells, their role in TSCM is not studied
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