Eomesodermin Increases Survival and IL-2 Responsiveness of Tumor-specific CD8+ T Cells in an Adoptive Transfer Model of Cancer Immunotherapy

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Abstract

Tumor-specific CD8+ T cells often fail to elicit effective antitumor immune responses due to an inability to expand into a substantial effector population and persist long-term in vivo. Using an adoptive transfer model of cancer immunotherapy, we demonstrate that constitutive eomesodermin (Eomes) expression in tumor-specific CD8+ T cells improves tumor rejection and survival. The increase in tumor rejection was associated with an increased number and persistence of CD8+ T cells in lymphoid tissues during acute tumor rejection, tumor regrowth, and in mice that remained tumor-free. Constitutive Eomes expression increased expression of CD25, and this was associated with enhanced interleukin-2 responsiveness and tumor-specific CD8+ T-cell proliferation. Moreover, constitutive Eomes expression improved cell survival. Taken together, our data suggest that constitutive Eomes expression enhances CD8+ T-cell proliferation and survival, in part through the enhancement of interleukin-2 responsiveness through CD25 induction.

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