Tumor rejection in Cblb-/- mice depends on IL-9 and Th9 cells
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ABSTRACT: Casitas B lymphoma-b (Cbl-b) is a central negative regulator of cytotoxic T and NK cells, explaining its intracellular checkpoint function in cancer. Increasing evidence highlights the importance of CD4+ T helper cell populations (e.g., IL-9 producing T cells: Th9 cells) for anti-cancer immunity. We here provide experimental evidence that Cbl-b acts as rheostat favoring regulatory T cells (Treg) at the expense of Th9 cell differentiation. Adoptively transferred tumor-model antigen specific Cblb-/- Th9 cells exert superior anti-tumor activity leading to improved melanoma control in vivo. Accordingly, blocking IL-9 in melanoma cell-exposed Cblb-/- mice reverses their tumor rejection phenotype. Single cell RNA sequencing of in vitro differentiated Th9 cells from naïve T cells isolated from WT and Cblb-/- animals revealed the transcriptomic basis for increased Th9 cells differentiation. In summary, we here first establish IL-9 and Th9 cells as key anti-tumor executers in Cblb-/- animals. This knowledge may be helpful for future improvement of adoptive T cell therapies in cancer.
ORGANISM(S): Mus musculus
PROVIDER: GSE173395 | GEO | 2022/04/30
REPOSITORIES: GEO
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