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Published on: June 12, 2021
Eomesodermin Increases Survival and IL-2 Responsiveness of Tumor-specific CD8+ T Cells in an Adoptive Transfer Model
Aki Furusawa1,2, John Reiser1,2, Kavitha Sadashivaiah1,2
1Program in Oncology, Marlene and Stewart Greenebaum Comprehensive Cancer Center, Center for Stem Cell Research and Regenerative Medicine.
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.
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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