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Inhibition of salt inducible kinases reprograms T cells and antitumor immunity in ovarian cancer

GSE275654 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2026/03/31 Platform GPL24247
Summary
Patients with metastatic high grade serous ovarian carcinoma (HGSOC) are often unresponsive to immunotherapies; here, we identify salt-inducible kinases (SIK) as a key driver of immunosuppression. Human T cells in the presence of patient ascites express high levels of SIK and the upstream kinase LKB1, while SIK inhibition reprograms human T cells and strongly activates antitumor responses. In syngeneic mice with resistant HGSOC, genetic ablation and pharmaceutical inhibition of SIK consistently demonstrated therapeutic efficacy and survival advantages, and combination of PD-1 blockade with SIK inhibition further extended survival. We identified a major role of T cell-intrinsic SIK2/3 signaling in driving immunosuppression in part by TXNIP induction and LYST suppression. Multi-omics analyses on SIK inhibitor therapy revealed reduced disease progression, increased T cell infiltration with enhanced cytotoxicity and effector cytokine IFN-g, and a shift from immunosuppressive to immunostimulatory cellular niche. We propose SIK inhibitors as a new immunotherapy.
Published in
Inhibition of salt-inducible kinases reprograms T cells and antitumor immunity in ovarian cancer
Dong H, Ray A, Rotter LK et al. · Nature immunology 2026 · PMID 42162294 · doi:10.1038/s41590-026-02512-8
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Also filed as BioProject PRJNA1152508 and SRA study SRP528621. Searching any of these in the dataset finder brings you back here.

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