GSE266219 Clinical and Immunological Responses to Combined JAK Inhibition and PD-1 immunotherapy for Lung Cancer Patients

Contributors : Divij Mathew ; Andy MinnSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensPersistent inflammation driven by cytokines like type-one interferon (IFN-I) can cause immunosuppression. We show that administration of the JAK1 inhibitor itacitinib after anti-PD1 immunotherapy improves immune function and anti-tumor responses in mice, and results in high response rates (67%) in a phase-2 clinical trial for metastatic non-small cell lung cancer. Patients who failed to respond to initial anti-PD1 immunotherapy but responded after addition of itacitinib had multiple features of poor immune function to anti-PD1 alone that improved after JAK inhibition. Itacitinib promoted CD8 T cell plasticity and therapeutic responses of exhausted- and effector-memory-like T cell clonotypes. Patients with persistent inflammation refractory to itacitinib showed progressive CD8 T cell terminal differentiation and progressive disease. Thus, JAK inhibition may improve the efficacy of anti-PD1 immunotherapy by pivoting T cell differentiation dynamics.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research