KDM5 histone demethylases repress immune response via suppression of STING
Fig 7
KDM5B is negatively associated with STING expression, CD8+ T-cell infiltration, and clinical outcome.
(A) Anticorrelation between expression of KDM5B and STING in TCGA cancer samples. Normalized STING levels in “KDM5B low” and “KDM5B high” samples of breast invasive carcinoma, bladder urothelial carcinoma, and ovarian serous cystadenocarcinoma from the TCGA datasets. The numerical values used to generate these graphs are available in S1 Data. (B) Correlation between KDM5B and STING in HPV+ head and neck tumors. n = 79. (C) Correlation between KDM5B and CXCL10 (left panel) or STING and CXCL10 (right panel) in HPV+ head and neck tumors. (D) Correlation between KDM5B expression and CD8+ T-cell infiltration in HNSC-HPVpos. (E) Association of CD8+ T-cell infiltration level (left panel) and KDM5B expression (right panel) with survival of HPV+ head and neck cancer patients. Tumors in the top 25th percentile were compared to those in the bottom 25th percentile. (F) A working model for how KDM5i induces innate and adaptive immune responses. HPV, human papilloma virus; HNSC-HPVpos, HPV+ head and neck tumors; ISRE, interferon-stimulated response element; KDM5i, KDM5 inhibitor; STING, stimulator of interferon genes; TCGA, The Cancer Genome Atlas.