Extended Data Fig. 2: Chemotherapy activates STING-IFN-I pathway to enhance antigen presentation capacity of cancer cells.
a, In situ CD20+ B cell density in matched NPC tumors before and after chemotherapy. b, UMAP plot showing 13 clusters of tumor cells colored by patient identity (left) and treatment status (right). c, Expression of MHC classI and antigen presentation genes of individual tumor cells from each patient in the single-cell dataset. Matched samples with > 20 malignant cells were included in the analysis (n = 8 pairs). P values for samples with significantly increased antigen presentation molecules after chemotherapy were shown. d, Kaplan–Meier curves for DFS in NPC patients stratified by high versus low expression of signature scores for trajectory_I (Cluster_12) in Cohort_2. Patients were dichotomously divided based on median expression values. HRs and 95% CIs were calculated using a Cox regression model (two-sided P value by log-rank test). e, Changes of phospho-STAT1 after chemotherapy in NPC samples from Fig. 1d. f,g, IFN-β level (f), phospho-STAT1 (g) in HONE1 treated with GEM, DDP, or GP (48 h; n = 3). h-k, Expression of MHC classI and antigen presentation genes in HK1 (h,k) and HONE1 (i,j) treated with GEM, DDP, or GP (48 h; n = 3). l, Changes in tumor cell STING expression after chemotherapy in the single-cell dataset. Samples with increased MHC classI in c were included in the analysis (n = 5 pairs). The bottom and top of the boxes were 25th and 75th percentiles, respectively (interquartile range). Whiskers encompassed 1.5 times the interquartile range. m, Phospho-STING, STING, phospho-TBK1, TBK1, phospho-IRF3, and IRF3 in HONE1 treated with GEM, DDP, or GP (48 h, n = 3). n, MHC classI and antigen presentation gene expressions in STING knock-out HK1 treated with or without GP chemotherapy (48 h; n = 3). o-q, STING expression (o,p), IFN-β level (p), phospho-STING, phospho-STAT1 (p), MHC classI and antigen presentation gene expression (q) in STING knock-down HONE1 treated with or without GP chemotherapy (48 h; n = 3). Data are the mean ± s.d. A two-sided Wilcoxon test was computed for (c,l), a two-sided one-way ANOVA followed by LSD test for multiple-comparison was computed for (f,h-j,n,o-q).
