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Aspirin prevents metastasis by limiting platelet TXA2 suppression of immunity
Inhibition of cyclooxygenase 1 releases T cells from immunosuppression by platelet-derived thromboxane A2, thereby enhancing the immune response against metastasis.
Meta-analyses of large randomized controlled trials have shown that daily aspirin treatment is associated with reduction in metastasis at multiple sites in individuals with cancer 6(hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.48–0.84). In brief, Flow Cytometry Standard (FCS) 3.0 files were first imported in FlowJo version 10.10.0 to eliminate dead cells by manual gating, and select CD45+ leukocytes, subjected to biexponential transformation, then exported for computational analysis by a custom-made script making use of PhenoGraph (K value set at 30). In brief, three different sgRNAs targeting Tbxa2r: 5′-CCAGAGAAGCTCATGACAGG-3′, 5′-UUAGGAGCCAUGUGGCCCAA-3′ and 5′-CGAGGUGCCAUUGGGCCACA-3′ or their negative control: scrambled sgRNA#1 (Synthego) were incubated with Alt-R S.p.HiFi Cas9 Nuclease V3 Cas9 (Integrated DNA Technologies) to form sgRNA–Cas9 ribonuclear protein complexes before electroporating into naive MACS-sorted CD8+ T cells labelled with CTV using a Lonza 4D-Nucleofector system (DS137).
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