Fig 1: HNSCC patients with ABCB11 high expression showed reduced PFS and OS after PD-1/PD-L1 inhibitors therapy. (A) The volcano map of differentially expressed genes in “response” group and “no response” group. The Kaplan-Meier survival analysis was used to analyze the OS and PFS of patients with different expression level of the (B) FOXA2, (C) SLC28A and (D) ABCB11 after PD-1/PD-L1 inhibitors therapy. The expression of ABCB11 was compared in HNSCC patients with different response to PD-1/PD-L1 inhibitors therapy in (E) GEO cohort and (F) Mendeley Data cohort. (G) The correlations of age, sex, tobacoo and alcohol states with ABCB11 expression in GEO cohort.
Fig 2: CYP1A2 expression was significantly upregulated in CD45+ABCB11+ TILs compared with CD45+ABCB11-TILs. (A) The gene expression of CYP enzymes between tissues with ABCB11 high expression and those with ABCB11 low expression in (A) GEO dataset and (B) TCGA database. (C) Representative flow cytometry plots showing the process for sorting CD45+ABCB11+ TILs and CD45+ABCB11-TILs in NHSCC tissues. (D) Western bolt analysis of CYP1A2 expression in CD45+ABCB11+ TILs and CD45+ABCB11-TILs in HNSCC tissues.
Fig 3: ABCB11 participated in xenobiotic metabolic process and was associated with immunosuppressive cells infiltration. GO enrichment analysis of the pathways enriched in tissues of ABCB11 high expression compared with ABCB11 low expression in (A) GEO dataset and (B) TCGA dataset respectively. GSEA enrichment analysis of the pathways about metabolism of xenobiotics by cytochrome P450 and cytokine-cytokine receptor interaction in HNSCC tissues with ABCB11 high expression compared with those with ABCB11 low expression in (C) GEO dataset and (D) TCGA database. ImmuCellAI web tool was used to estimate the immune cell infiltration in tissues with ABCB11 high expression compared with tissues with ABCB11 low expression in (E) GEO dataset and (F) TCGA database.
Fig 4: Colocalization of ABCB11 and CYP1A2 in immature TLSs had positive correlation with immunosuppressive Treg cells infiltration. (A-B) Representative images of ABCB11+CYP1A2+ immature TLS and ABCB11-CYP1A2- mature TLS in HNSCC tissues. (C) The CYP1A2 expression pattern in tissues with ABCB11+ TLSs and tissues with ABCB11-TLSs. (D) FOXP3+ Treg infiltration in tissues with ABCB11+CYP1A2+ TLSs and tissues without ABCB11+CYP1A2+ TLSs.
Fig 5: ABCB11 was accumulated in immature TLSs of NHSCC tissues. Representative images of ABCB11+ immature TLS and ABCB11— mature TLS in HNSCC tissues.
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