Extended Data Fig. 4: A non-immunosuppressive tumor microenvironment and activated circulating CD8 T cells before treatment are associated with survival in mPDAC patients treated with nivo/chemo.

a, Heatmap showing results of unsupervised clustering of gene expression signatures and survival status in the nivo/chemo arm. Individual patients are shown in columns and annotated by survival status at 1 year to illustrate association. Gene expression signature labels are color coded based on survival association by log-rank test. KM curves for overall survival stratified by median values at baseline of b, TNF-α via NFκB hallmark pathway signature score and c, Percentage of iNOS+ intratumoral macrophages out of total cells from mIF (c, top panel). Representative pretreatment tumor mIF images showing iNOS+ cells from two patients with labels showing marker grouping (low = below median, high= above median) and individual patient survival (c, bottom panel). d, Spearman correlation matrix of tumor immune populations and gene expression signatures in pretreatment tumor biopsies, with labels color coded by association with survival association by log-rank test. Note the Y-axis labels are to be repeated along the X-axis (bottom to top on Y-axis corresponding to left to right on X-axis). e, Multi-omic dimensionality reduction of circulating factors and tumor data using Independent Component Analysis, with each dot representing a single patient colored by survival status at one year and with position determined by reduced dimensionality across all tumor and circulating biomarkers. Black separating line serves to illustrate a separation and is not computationally derived. On all KM curves, median values were determined using all data across the 3 arms, P-values are from a log-rank test between groups, and shaded regions illustrate 95% CI.