Fig. 4: Changes in the tumor immune microenvironment associated with intratumoral bacteria burden.
a, Correlation coefficients of TBB determined from WGS with immune cell populations in HNSCC tumors. Statistical analysis was conducted using a two-tailed Spearman correlation. Highlighted values indicate an FDR < 0.05 (n = 157). TFH cells, T follicular helper cells; TCM cells, central memory T cells. b, Correlation coefficients of TBB determined from WES in independent samples not analyzed by WGS (excluding samples from a) with immune cell populations in HNSCC tumors. Statistical analysis was conducted using a two-tailed Spearman correlation. Highlighted values indicate an FDR < 0.05 (n = 348). c, Correlation coefficients of TBB with immune cell populations in tumors from CIAO trial. Statistical analysis was conducted using a two-tailed Spearman correlation. Highlighted values indicate P < 0.05 (n = 28). d, Correlation of TBB with log-transformed tNLR in samples from CIAO trial. Statistical analysis was conducted using a two-tailed Spearman correlation (n = 28). e, Comparison of log-transformed tNLR between responders (PR) and nonresponders (SD and PD) from CIAO trial. Data are shown as the mean and 95% confidence interval. Statistical analysis was conducted using a two-tailed Welch’s t-test (nonresponder, n = 16; responder, n = 12). f, Spearman correlation coefficients of TBB with tNLR across cancer types for HNSCC by WGS (n = 157) and WES (n = 503), STAD by WGS (n = 114) and WES (n = 413), ESCA by WGS (n = 62) and WES (n = 183) and COADREAD by WGS (n = 155) and WES (n = 582). Statistical analysis was conducted using a two-tailed Spearman correlation. g–i, Correlation of imaging-based quantification of bacteria by 16S rRNA in situ hybridization with T cells detected by CD3 (g), neutrophils detected by CD66b (h) and difference between neutrophils and T cells (i). Inset values indicate the two-tailed Spearman correlation coefficient (n = 17). j, Changes induced by in vitro exposure of HNSCC cell lines to either Fusobacterium or Prevotella, with each dot representing an individual gene. Four separate cell lines were exposed to bacteria and the average fold change is shown. The inset value indicates the two-tailed Pearson correlation coefficient. Values represent the average of n = 4 cell lines, each analyzed in duplicate. k, Comparison correlation coefficients between individual genes and TBB in participant tumors (n = 503) with average change induced by in vitro exposure of HNSCC cell lines to Fusobacterium and Prevotella (n = 4 cell lines). In a–c, immune populations were determined by ssGSEA using signatures from Bindea et al.63,64.
