Fig. 3 |. Fecal microbial signatures are differentially associated with immune-related adverse events and progression-free survival in PD-1-treated patients with melanoma.

a, t-UMAP plot depicting compositional differences between patients with melanoma who developed any irAEs and those who did not at any time point from the start of anti-PD-1 therapy. Two-tailed P value was calculated using PERMANOVA. b, Heat map of differentially abundant taxa (P < 0.05 and FC > 2) in patients with no irAEs versus grade 1–4 irAEs. irAE severity was graded with CTCAE v5.0. The column on the left shows HRs on a color scale and Storey’s q value numerically when less than 0.1 for each LKT. Columns in the heat map depict patients grouped by reported or non-reported irAEs and clustered within corresponding groups based on gut microbiome composition. Rows depict bacterial taxa enriched (black) or depleted (red) in patients with melanoma with irAEs (grade 1–4) and clustered based on gut microbiota composition. Statistical significance was calculated by two-tailed Mann–Whitney U test. c, Percentages of PD-1-treated early-cohort patients with melanoma exhibiting all or specific types of irAEs segregated by relative abundance of the seven Streptococcus spp. identified in b (eight patients clustered in the high Streptococcus group; χ², *P = 0.0018; ***P = 0.001) d, Kaplan–Meier plot of PFS probability based on the relative abundance of Streptococcus spp. among patients with irAEs (n = 39). Numbers of patients at risk at each time point are shown. HR and score (log rank) test two-tailed P value from Cox proportional hazards regression analysis. e, Proportion of patients with melanoma treated with PPIs among patients with high versus low relative abundance of Streptococcus spp.