Transcriptomics,Genomics

Dataset Information

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Anti-inflammatory drugs remodel the tumor immune environment to enhance immune checkpoint blockade efficacy [SZ9]


ABSTRACT: Identifying strategies to improve the efficacy of immune checkpoint blockade (ICB) remains a major clinical need. Here, we show that therapeutically targeting the COX-2/PGE2/EP2-4 pathway with widely used non-steroidal and steroidal anti-inflammatory drugs synergized with ICB in mouse cancer models. We exploited a bilateral surgery model to harness the heterogeneity in treatment outcome and distinguish responders from non-responders shortly following treatment. Deep cellular and molecular tumor profiling revealed acute IFN-γ-driven tumor remodeling in responder mice that was also associated with patient benefit to ICB. Crucially, monotherapy with COX-2 inhibitors or EP2-4 PGE2 receptor antagonists rapidly induced this response program and, in combination with ICB, increased the intratumoral accumulation of T cells with enhanced effector function. Inhibition of the COX-2/PGE2 pathway in patient-derived tumor fragments from multiple patients and cancer types revealed a similar shift in the tumor inflammatory environment to favor T cell activation. Our findings establish the COX-2/PGE2/EP2-4 axis as an independent immune checkpoint and a readily translatable strategy to switch the tumor inflammatory profile from cold to hot and enhance the efficacy of immunotherapy. Overall design: Bulk RNA profiling of CT26 colorectal tumours treated with vehicle, celecoxib (CXB), anti-PD-1 or anti-PD-1 plus celecoxib for 7 days.

INSTRUMENT(S): Illumina NextSeq 500 (Mus musculus)

ORGANISM(S): Mus Musculus

SUBMITTER: Agrin Moeini  

PROVIDER: GSE160785 | GEO | 2021-09-13

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
GSE160785_SZ9_log2CPM_matrix.txt.gz Txt
GSE160785_SZ9_raw_count_matrix.txt.gz Txt
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