Fig. 5
Slamf9 mediates high H3K4me3-RS-related ICB therapy resistance in melanoma. A Sequencing of the expression log-fold change (log[FC]) value of genes in anti-CTLA4-resistant B16 murine tumors. The gene set is derived from the overlapping genes between the intersecting H3K4me3-RS-associated genes in the four cancer types (SARC, KIRC, SKCM, LUAD, p < 0.01, |r|> 0.1, Supplemental Table 4) and the DEGs between anti-CTLA4-resistant and parental murine B16 tumors [58]. B, C The Kaplan–Meier plot for the survival status of advanced clear cell renal cell carcinoma B and metastatic urothelial cancer C patients stratified by SLAMF9 expression level [48, 55]. The bar plot shows the proportion of patients with various ICB responses in the high and low SLAMF9 subgroups. D Comparison of Slamf9 expression level between anti-CTLA4-resistant and parental B16 murine tumors. Each dot represents a sample; the middle line represents the median expression value; the top and bottom of the boxes are the 75th and 25th percentiles (interquartile range), and the whiskers encompass 1.5 times the interquartile range. (E) The differentially expressed IFN-related genes in SLAMF9 knockout vs wild-type plasmacytoid dendritic cells. F, G The tumor volume curve and the final tumor weight after subcutaneous injection of the Slamf9-NC (n = 12) or Slamf9-knockdown (n = 12) B16F10 cells on C57BL/6 mice. H The representative image of immunofluorescent staining for tumor tissues from the Slamf9-NC and Slamf9-knockdown subcutaneous tumor model (F–G). The white fluorescence is CD8, the green fluorescence is CD3, and the red fluorescence is PD-1. The right bar plot for the number of cells stained by different fluorescences. (I) The schematic diagram of dosing regimen in Slamf9-knockdown or not B16F10 tumor-bearing mice. J, K Kaplan–Meier survival plots for Slamf9-NC (n = 24) or Slamf9-knockdown (n = 24) B16F10 tumor mice model. Randomly selecting mice for either anti-CTLA-4 inhibitor (n = 12) or anti-PD-L1 antibody (n = 12) treatment in the two groups respectively