Fig. 6: Caspase-1 inhibition recalibrates neutrophil-to-lymphocyte ratio and T cell activation. | Nature Communications

Fig. 6: Caspase-1 inhibition recalibrates neutrophil-to-lymphocyte ratio and T cell activation.

From: Chemotherapy-induced activation of caspase-1 and IL-1α release by cancer cells remotely skews myelopoiesis to drive pro tumorigenic systemic neutrophil-dominant inflammation

Fig. 6: Caspase-1 inhibition recalibrates neutrophil-to-lymphocyte ratio and T cell activation.The alternative text for this image may have been generated using AI.

a Representative immunofluorescence staining of neutrophils (Ly6G; red) and T-cells (CD8; green) in tumors from mice treated with vehicle, gemcitabine-cisplatin chemotherapy (Chemo), VX-765 caspase-1 inhibitor (Casp1i) + Chemo combination, and Casp1i. b Quantification of neutrophil (Ly6G+) to lymphocyte (CD8+) ratio (NLR) in tumors from mice treated with vehicle (17 random AOI from 7 mice), chemo (14 random AOI from 7 mice), Casp1i + Chemo combination (14 random AOI from 7 mice), and Casp1i (8 random AOI from 7 mice), respectively. Flow cytometry results quantifying percent of CD107a and interferon-gamma (IFNγ) expressing CD8+ T cells (c), and percent of CD107a and granzyme B (Gzmb) expressing CD8 + T cells (d) in tumors of mice treated with vehicle [black], gemcitabine-cisplatin chemotherapy (Chemo) [red], VX-765 caspase-1 inhibitor (Casp1i) + Chemo combination [teal], and Casp1i [blue], respectively (n = 5 mice per group). e Expression of immunosuppressive genes CD27, CD47 and S100A9 within the neutrophil population from vehicle, chemotherapy and chemotherapy + Casp1i treated tumors (n = 2 mice per group, 31,362 number of cells analyzed). f Expression of immunosuppressive genes CD274 and S100A9 in neutrophils of responder (n = 1) and non-responder (n = 1) patient tissues analyzed with Xenium from Fig. 1o. g Tumor growth kinetics of mice harboring G69 tumors treated with vehicle [black], chemotherapy (Chemo; Gemcitabine: 60 mg/kg, Cisplatin: 6 mg/kg) [red], Anti-IL-1α + Chemo combination (Anti-IL-1α: 200 μg/mouse) [teal], and Anti-IL-1α [blue] (n = 5 mice per group). h Representative immunofluorescence staining of tumor sections for CD8+ T cells (CD8; green) and neutrophils (Ly6G; red) in vehicle, gemcitabine-cisplatin chemotherapy (Chemo), Anti-IL-1α + Chemo combination, and Anti-IL-1α. Statistics: Ordinary one-way ANOVA follow by Dunnett’s multiple comparison test (b–d) and two-way ANOVA with Geisser-Greenhouse correction followed by Dunnett’s multiple comparison test (g) were performed. Error bars represent standard error of mean (s.e.m.) unless otherwise stated. Source data are provided as a Source Data file.

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