Fig. 8: Observed patterns of aITH indicate benign adenomas (CRA) are highly antigenic and remain under immune control, while colorectal carcinomas (CRC) have escaped elimination via immune suppression.

Sample sizes are n = 6 CRA, n = 3 “carcinoma-in-ad” (CIA = A-CIA and C-CIA), and n = 7 CRC. In the boxplots shown in a, b, the center line of each boxplot indicates the median, the top and bottom of the box indicate the 75th and 25th percentiles, respectively, the top whisker the largest value that is no further than 1.5 Interquartile range (IQR) from the 75th percentile, the bottom whisker the smallest value no more than 1.5 IQR from the 25th percentile, and points indicate outliers. a Distribution of neoantigen recognition potentials (RP), weighted by their variant allele frequency (VAF). Comparisons across groups indicate that currently benign CRA are significantly more antigenic than all other tumor types, as determined using Dunn’s test of multiple comparisons using rank sums. b CRC have significantly higher neoantigen burdens than all other cell types, and modeling indicates that this occurs when selection against antigenicity is relaxed due to immune suppression. c For the samples in which there was both imaging and genomics (n = 2 CRA, n = 1 CIA, n = 3 CRA, each with 10 downsampled replicates, thereby normalizing for sequencing depth), principal component analysis (PCA) of all cell/environmental markers, neoantigen burden, and weighed recognition potentials reveals that CRA is highly antigenic and inflammatory, while CRC is associated with immunosuppressive cells and high neoantigen burden.