Fig. 6: ISM5939 augments antitumor immunity and synergizes with anti-PD(L)1 immunotherapy. | Nature Communications

Fig. 6: ISM5939 augments antitumor immunity and synergizes with anti-PD(L)1 immunotherapy.

From: Oral ENPP1 inhibitor designed using generative AI as next generation STING modulator for solid tumors

Fig. 6

A Baseline ENPP1 expression levels in Paclitaxel+anti-PD1 responsive or non-responsive breast cancer patients (GEO: GSE194040). n = 38 for responders and n = 31 for non-responders. B Baseline ENPP1 expression levels in anti-PD-L1 responsive or non-responsive esophageal adenocarcinoma patients with high LRRC8A expression. Data were extracted from GSE165252. n = 6 for responders and n = 3 for non-responders. For boxplots, boxes indicate 25th and 75th percentiles, the lines within boxes mark medians, whiskers extend over 1.5 times the interquartile range (IQR, the distance from 25th to 75th percentile); dots represent patient samples. C Combinational effect of ISM5939 and anti-PD-L1 therapy. MC38 tumor‐bearing C57BL/6 J mice were treated with anti‐PD‐L1 antibody (3 mg kg−1, twice per week) alone or in combination with ISM5939 (30 mg/kg, twice a day) for indicated days (n = 6 biological replicates per group). D Combinational effect of ISM5939 and anti-PD1 therapy. MC38 tumor‐bearing C57BL/6 J mice were treated with anti‐PD1 antibody (5 mg kg−1, twice per week) alone or in combination with ISM5939 at the indicated doses (n = 8 biological replicates per group). E–H Tumor infiltrating immune cells analyzed by flow cytometry. MC38 tumor‐bearing C57BL/6 J mice were treated with anti‐PD1 antibody (5 mg kg−1, twice per week) alone or in combination with ISM5939 (20 mg kg−1, twice a day) for 7 consecutive days (n = 6 biological replicates). E, F The proportion of the indicated immune cells in tumor infiltrating CD45+ cells; G The ratio of CD8+ T cells (left) and CD4+ T cells (right) to Tregs. H CD69 positive ratios among the indicated immune subsets. I Tumor growth of CT26 syngeneic tumors. Tumor bearing mice (n = 6 biological replicates per group) were treated with anti-PD1 antibody alone or in combination with ISM5939 (20 mg kg−1, twice a day). Data are represented as mean ± SEM. For (A, B) and (E–G), data were analyzed by two‐tailed Student’s t‐test. P value < 0.05 were shown. Data were represented as mean ± SEM. Source data are provided as a Source Data file.

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