Figure 1
IL23A was significantly upregulated by chemotherapy and associated with a favorable prognosis in TNBC patients. (A) The whole transcriptomic sequencing of TNBC cells treated with chemotherapeutic drugs. Upper panel, the experimental design. Lower panel, overlapping immune- and secretome-related genes, and significantly affected genes in TNBC cells treated with chemotherapeutic drugs (log2|Fc|≥ 2, P < 0.05). (B) Heapmap of 18 genes identified in Fig. 1A, ranked by normalized log2Fc. IL23A was identified as the most upregulated gene in response to chemotherapeutic drugs. (C) mRNA levels of two subunits of IL-23 (IL23A and IL12B) in TNBC cells treated with chemotherapeutic drugs, detected by qRT-PCR. (D) Protein expressions and quantifications of IL-23 in TNBC cells treated with chemotherapeutic drugs, detected by western blot. The PVDF membranes were cropped at 35 kDa before antibody incubation. Original blots are presented in Supplementary Fig. S6. (E) Left panel, representative immunohistochemistry (IHC) staining of IL-23A and CD8 on resected tumor tissues from TNBC patients who did (n = 27) or did not (n = 37) receive neoadjuvant chemotherapy. Scale bars 50 μm. Middle and right panel, quantitative analysis. (F) Spearman correlation analysis revealing a correlation between IL-23A staining score and CD8 + T cell counts in resected tissues from TNBC patients (n = 64, r = 0.465, p = 0.0001). (G) Upper panel, representative CT scans before and after neoadjuvant chemotherapy from one of the patients whose resected tumor tissues exhibited high scores of IL-23A staining, as well as the representative IHC staining. Scale bars, 50 μm. Lower panel, the slope chart shows the overall response rate (ORR) of TNBC patients who received neoadjuvant chemotherapy (n = 22). Blue bars represent patients from the IL-23Alow group with an IL-23A IHC score of 0–6 (n = 8); Red bars represent patients from the IL-23Ahigh group with an IL-23A IHC score of 7–12 (n = 14). (H) The correlation between IL23A mRNA levels and overall survival of patients with breast cancer (HR = 0.73, P = 0.0048, left panel) or Triple-negative breast cancer (HR = 0.22, P < 0.0001, right panel). Data from the Kaplan–Meier plotter database (https://www.kmplot.com/). Error bars represent standard deviation (SD), *P < 0.05; **P < 0.01; ****P < 0.0001.
