Fig. 2

Alterations of gut microbial composition with different irAEs status among three anti-PD-1/PD-L1 cohorts. A Variance explained by irAEs status (irAEs versus non-irAEs) is plotted against variance explained by study effects for individual ASVs. The significantly differential ASVs are colored in red and the dot size is proportional to the abundance of each ASV. P values were from a two-sided blocked Wilcoxon rank-sum test. B Relative abundance of bacterial phyla in irAEs and non-irAEs across all three different studies. C Alpha diversity analysis calculated with Fisher alpha, Richness, Shannon, and Simpson indexes. D Principal coordinate analysis of samples (irAEs: n = 77; non-irAEs: n = 113) from all three anti-PD-1 studies based on Bray–Curtis distance. P values of beta diversity based on Bray–Curtis distance were calculated with PERMANOVA. The study is color-coded and the group (irAEs and non-irAEs) is indicated by different shapes. The upper-right and the bottom-left boxplots illustrate that samples projected onto the first two principal coordinates broken down by study and disease status, respectively. P values of the first and second principal components were calculated with a two-sided Kruskal–Wallis test for study and group. All boxplots represent the 25th–75th percentile of the distribution; the median is shown in a thick line at the middle of the box; the whiskers extend up to values within 1.5 times of IQR, and outliers are represented as dots. The anti-PD1/PD-L1 cohorts comprising over 50 patients, such as those led by Zhang et al., Hakozaki et al., and McCulloch et al., were utilized for the analysis in this part