Fig 2: Negative correlation among apCAFs, CD8+ T cells and IFN‐γ +CD4+ T cells in pancreatic cancer. A) The represent graph of the expression of MSLN, CD8, CD74, and PDGFα by multiple immune fluorescent staining in tissue microarray, respectively. Scale bar = 100 µm. B) The represent graph of the expression of IFN‐γ, CD4, CD74, and PDGFα by multiple immune fluorescent staining of tissue microarray. Scale bar = 100 µm. C) The correlation analysis between MSLN expression and apCAF. D) The correlation analysis between apCAFs and CD8+ T cells. E) The correlation analysis between apCAFs and IFN‐γ +CD4+ T cells.

Fig 3: Persistent challenges with either oxLDL or free cholesterol are required to sustain low-grade inflammation in cultured monocytes. (A–B) Murine bone marrow monocytic cells (BMMCs) were stimulated with oxidized low-density lipoprotein (OxLDL, 10 μg/ml) or PBS for either 5 h (5H) or 5 d (5D). (C–D) BMMCs were stimulated with cholesterol (Chol, 10 μg/ml) or ethanol (vehicle control) for either 5 hours (5H) or 5 days (5D). The expression levels of CD49d, CD74, CD86, and CD38 were evaluated by flow cytometry, and mean fluorescence intensity (MFI) of each molecule is displayed. Statistical analysis was performed using 2-way ANOVA followed by Tukey’s multiple comparison test (n=3 per group). Data represent mean ± standard deviation (SD) (**P < 0.01, *** P < 0.001; NS, not significant).

Fig 4: Fumagillin and DHA alleviate the low-grade inflammation phenotype in monocytes. (A–H) BMMCs were treated with OxLDL or cholesterol in the presence of fumagillin (Fuma, 10 ng/ml) for 5 d. (I–P) BMMCs were treated with OxLDL or cholesterol in the presence of docosahexaenoic acid (DHA, 60 μM) for 5 d. The expression levels of CD49d (A, E, I, M), CD74 (B, F, J, N), CD86 (C, G, K, O), and CD38 (D, H, L, P) were evaluated by flow cytometry, and MFI of each molecule is displayed. Statistical analysis was performed using 1-way ANOVA (n=3 per group). Data represent mean ± standard deviation (SD) (*P < 0.05, ** P < 0.01, *** P < 0.001; NS, not significant).

Fig 5: CDK4/6 inhibition triggers MIF‐induced functional reprogramming of TAMs. a,b) Cell–cell communication between tumor cells and intratumoral M1 and M2 macrophages a) and interaction strength of MIF bound to CD44/CD74 complex from tumor cells to M1 and M2 macrophages b) in Balb/c mice orthotopically implanted with 4T1 tumors after control or abemaciclib treatment. c) Representative immunoblots and fold changes in MIF expression in control‐ or abemaciclib‐treated 4T1 cell debris and supernatant. d) Representative immunoblots and fold changes in MIF expression in control‐ or abemaciclib‐treated tumor cell debris from 4T1 or HP5712:BM‐M1 macrophages in the Transwell model. e) Representative images and quantification of MIF expression (green) in control‐ or abemaciclib‐treated FVB mouse BM‐M1 macrophages from HP5712:BM‐M1 in the Transwell model (5 areas × 4 samples, for each); scale bar = 100 µm. f) Representative FACS plots and quantification of the proliferation potential of Balb/c mouse BM‐M1 macrophages cocultured with 4T1 after pre‐DMSO plus abemaciclib or pre‐4‐IPP plus abemaciclib treatment in the con‐treatment model (n = 3, for each). g) Representative FACS plots and quantification of TNFα expression on Balb/c mouse BM‐M1 macrophage cocultured with 4T1 after pre‐DMSO plus abemaciclib or pre‐4‐IPP plus abemaciclib treatment in the con‐treatment model (n = 6, for each). h) Representative images and quantification of MIF expression (green) in control‐ or abemaciclib‐treated FVB mouse BM‐M1 macrophages from HP5712‐sgMif:BM‐M1 in the Transwell model (10 areas × 4 samples, for each); scale bar = 100 µm. i) Representative FACS plots and quantification of TNFα expression on Balb/c mouse BM‐M1 macrophages cocultured with 4T1‐sgNc or 4T1‐sgMif after abemaciclib treatment in the con‐treatment model (n = 6, for each). j) Representative FACS plots and quantification of CD86 expression on Balb/c mouse BM‐M2 macrophages cocultured with 4T1‐sgMif after control or abemaciclib treatment in the con‐treatment model (n = 6, for each). k) 3D‐immunofluorescence (3D‐IF) quantification of F4/80‐positive, CD8a‐positive, and granzyme B‐positive cells in human TNBC tumor slices after pre‐DMSO plus abemaciclib or pre‐4‐IPP plus abemaciclib treatment (3 areas × 3 samples, for each). l) Representative immunoblots and quantification of HIF‐1α expression in control‐ or gradient concentrations of abemaciclib‐treated 4T1 cell debris. m) Concentration of secreted MIF in the supernatant from 4T1‐sgHif‐1α cells after control or abemaciclib treatment (n = 3, for each). n) Kyoto encyclopedia of genes and genomes (KEGG) terms for abemaciclib‐dysregulated genes in M1 macrophages within 4T1 tumors compared with control, as determined via scRNA‐seq. o) Gene ontology (GO) terms for abemaciclib‐downregulated genes in M1 macrophages within 4T1 tumors compared with control, as determined via scRNA‐seq. p) Representative immunoblots and quantification of NF‐κB and phosphorylated NF‐κB expression in BM‐M1 macrophages from tumor cell:BM‐M1 in the Transwell model. P‐values are calculated using unpaired two‐tailed t‐test e–k, m). Data presented as mean ± SD. ns, p > 0.05; * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.