Fig 2: Graphic abstract showing how the KPNA2/CBX8/PRDM1/c-FOS pathway works in BCa. The interaction of KPNA2 with CBX8 contributes to the development and progression of BCa by mediating the PRDM1/c-FOS pathway

Fig 3: KPNA2 contributes to the xenograft tumor growth of BCa in vivo by mediating the PRDM1/c-FOS pathway. a The curve displaying tumor volume at various time points. b The representative images of resected tumors and curve displaying tumor weight at various time points. c The expression of KPNA2, PRDM1 and c-FOS in transplanted tumor tissues determined by RT-qPCR. d The expression of KPNA2, PRDM1 and c-FOS in transplanted tumor tissues determined by Western blot analysis. e The tumor cell proliferation detected by EdU assay (×400). f The tumor cell apoptosis detected by TUNEL assay (×200). n = 12. * p < 0.05 vs. nude mice bearing T24 cells treated with oe-NC. #p < 0.05 vs. nude mice bearing T24 cells treated with oe-KPNA2

Fig 4: CBX8 recruits PRC1-BCOR to the PRDM1 promoter region to downregulate PRDM1 expression. a The correlation analysis between expression of CBX8 and PRDM1 in BCa according to GEPIA (p = 0.00017). b The box plot of PRDM1 expression in BCa samples (left red box) and normal samples (right grey box) according to GEPIA. *p < 0.05 vs. normal samples analyzed by paired t-test. c The silencing efficiency of sh-CBX8 determined by Western blot analysis. d The enrichment of CBX8 in the PRDM1 promoter region detected by ChIP assay. e The interaction between CBX8 and BCOR detected by co-IP. f The enrichment of BCOR in the PRDM1 promoter region detected by ChIP. g The relative luciferase activity determined by dual luciferase reporter assay. h The expression of PRDM1 in response to CBX overexpression/knockdown determined by RT-qPCR. i The expression of PRDM1 in response to CBX overexpression/knockdown determined by Western blot analysis. *p < 0.05 vs. T24 cells treated with sh-NC (panels c, d, f and g) or T24 cells treated with oe-NC (panels h and i); #p < 0.05 vs. T24 cells treated with sh-NC (panels h and i)

Fig 5: Blocking CSC‐mediated suppression of CD103⁺ T cells to inhibit NSCLC expansion. A) CD8⁺ T cells were preconditioned with PDOs for 24 h, followed by ex vivo induction of CD8⁺CD103⁺ T cells. Immunoblot analysis showed Blimp‐1 expression in induced T cells. Mean ± SEM from 3 individuals in each group. B,C) CD8⁺ and CD4⁺ T cells were co‐cultured for 24 h with PDOs pretreated with or without BMS‐303141 (40 µm) and an ACSS2 inhibitor (10 µm). The T cells were then isolated, activated, and induced to differentiate into CD103⁺ populations. Blimp‐1 protein levels in CD8⁺ T cells and the differentiation of CD8⁺CD103⁺, and CD4⁺CD103⁺ T cells were analyzed by immunoblotting and flow cytometry, respectively. Mean ± SEM from 3 individuals in each group. D) PDOs were transfected with shRNAs targeting ACLY and ACSS2 before the PDO‐PBMC coculture, and then the differentiation of CD8+CD103+ T cells was detected. Mean ± SEM from 5 individuals in each group. E) CD8+ T cells were incubated with PDOs for 24 h and then transfected with shRNAs against GCN5. Blimp‐1 protein in induced T cells was analyzed by immunoblotting. F,G) PDOs were treated with or without BMS‐303141 (40 µm) plus ACSS2 inhibitor (10 µm), then incubated with either control PBMCs or PBMCs pre‐transfected with GCN5 shRNA. PDO outgrowth was subsequently measured. Mean ± SEM from 4 individuals in each group. Scale bars, 200 µm. H,I) CD133‐expressing CSCs were isolated from PDOs, transfected with the indicated shRNAs, and reintroduced into the PDOs for subsequent PDO‐PBMC co‐culture. CD8+CD103+ T cells were assessed by flow cytometry. Mean ± SEM from 5 individuals in each group. J–M) CD133‐expressing CSCs were isolated from PDOs, transfected with the indicated shRNAs, and reintroduced into the parental PDOs. These reconstituted PDOs were then implanted into NSG mice, which were intravenously injected with patients’ PBMCs. Tumor growth and tumor‐infiltrating CD8+CD103+ T cells were subsequently analyzed. Mean ± SEM from 5 chimeras in each group. N,O) CD8+ T cells isolated from patient‐derived PBMCs were transfected with the indicated shRNAs and reintroduced into the PBMC population for immune reconstitution of PDO‐NSG chimeric mice. Tumor growth and tumor‐infiltrating CD8+CD103+ T cells were subsequently analyzed. Mean ± SEM from 5 chimeras in each group. P,Q) CD8+ T cells isolated from patient‐derived PBMCs were transfected with the indicated shRNAs and reintroduced into the PBMC population for immune reconstitution of PDO‐NSG chimeric mice treated with or without acetate. Tumor growth and tumor‐infiltrating CD8+CD103+ T cells were subsequently analyzed. Mean ± SEM from 5 chimeras in each group. **p < 0.01, ***p < 0.001, ****p < 0.0001 with paired t‐test H,I, K, M, O) and ANOVA plus Tukey's method D, G, J, L, N, P,Q).