Helios Limits CD8 T Cell Antitumor Capacity

Abstract Text: Helios (Ikzf2) is a transcription factor associated with suppressive function in thymic-derived CD4 regulatory T cells. Previously, we documented Helios expression in CD8 cells exposed to antigen presented as self or associated with malignant cells.
Here, we analyzed whether Helios is induced in tumor infiltrating CD8 T cells and determined the effects of its absence.
Helios expression was documented in CD8 T cells infiltrating tumors from patients with colorectal cancer. It showed a statistically significant correlation with tumor stage.
In mice with B16 melanoma, Helios upregulation was observed in tumor infiltrating CD8 T cells. Cells from tumor draining lymph nodes remained Helios negative. Helios was induced by antigen activation, as it was not observed in OT-I cells from tumors devoid of ovalbumin.
Helios deficiency in T cells (Cd4-Cre) and in CD8 T cells (E8III-Cre) decreased melanoma and colon adenocarcinoma growth in mice. This was associated with decreased abundance of terminally exhausted CD8 T cells and increased frequency of TCF-1+ cells.
We generated Pdcd1 and Ikzf2 double KO mice (dKO). dKO mice, controlled tumor growth better than mice with isolated deficiencies. Tumors did not grow in a large fraction of dKO mice. Tumor infiltrating CD8 T cells from dKO mice produced higher levels of IFN-g and granzyme B.
These results indicate that Helios is induced in CD8 T cells by the tumor microenvironment and that its presence curbs the anti-tumor capacity of CD8 T cells.