Comprehensive assessment of computational methods for cancer immunoediting.

Abstract

Cancer immunoediting reflects the role of the immune system in eliminating tumor cells and shaping tumor immunogenicity, which leaves marks in the genome. In this study, we systematically evaluate four methods for quantifying immunoediting. In colorectal cancer samples from The Cancer Genome Atlas, we found that these methods identified 78.41%, 46.17%, 36.61%, and 4.92% of immunoedited samples, respectively, covering 92.90% of all colorectal cancer samples. Comparison of 10 patient-derived xenografts (PDXs) with their original tumors showed that different methods identified reduced immune selection in PDXs ranging from 44.44% to 60.0%. The proportion of such PDX-tumor pairs increases to 77.78% when considering the union of results from multiple methods, indicating the complementarity of these methods. We find that observed-to-expected ratios highly rely on neoantigen selection criteria and reference datasets. In contrast, HLA-binding mutation ratio, immune dN/dS, and enrichment score of cancer cell fraction were less affected by these factors. Our findings suggest integration of multiple methods may benefit future immunoediting analyses.