Extended Data Fig. 2: Microbiota composition of non-progressing patients in the Pittsburgh cohort whose stool samples were collected 4–41 months after initiation of therapy is not predictive of late therapy failure but is enriched for similar bacterial taxa as observed in the initial microbiome of patients who did not progress at 10 months. | Nature Medicine

Extended Data Fig. 2: Microbiota composition of non-progressing patients in the Pittsburgh cohort whose stool samples were collected 4–41 months after initiation of therapy is not predictive of late therapy failure but is enriched for similar bacterial taxa as observed in the initial microbiome of patients who did not progress at 10 months.

From: Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1

Extended Data Fig. 2

a. Plot of time of stool sample acquisition from 31 patients whose samples were collected after >4 months from therapy initiation. b. Progressor (P) and non-progressor (NP) groups identified at serial timepoints after late stool collection (top panel) were used to calculate the significance (two-tailed p-value) of compositional differences of the late-collected fecal microbiome using PERMANOVA (bottom panel). Fecal microbiota composition was determined using metagenomic sequencing. Progression during continued therapy was evaluated using RECIST v1.1 every 3 months or by clinical observation during follow-up visits. Number of patients on follow-up at each timepoint in relation to response status is shown in top panel. c. t-distributed uniform manifold approximation and projection (t-UMAP) plot depicts fecal microbiota compositional differences between early-collected patients who progressed (red) or did not progress (blue) in the first 10 months after initiation of therapy and late-collected long-term responders (green). Distance between centroids calculated as described in Fig. 1a, and significance (two-tailed p-value) of the differences by PERMANOVA are shown in lower table. d. Heatmap shows differentially abundant taxa (p < 0.05 and FC > 2) between the late Pittsburgh cohort compared with Ps (top) and NPs (bottom) at 10 months from the early Pittsburgh cohort. Columns denote patients grouped by each cohort before clustering; rows denote bacterial taxa enriched (black) or depleted (red) in early-sampled P versus late-sampled long-term NP clustered based on microbiota composition. Two-tailed p-values were calculated using two-tailed Mann-Whitney U test. e. ROC curve for manual model trained on the organisms associated with increased and decreased PFS in the Pittsburgh cohort from Supplementary Tables 4 and 5. Note that the model predicts late Pittsburgh samples well even though they were not included in the data used in training.

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