Comprehensive assessment of computational methods for cancer immunoediting

Area of Science:

• Immunology
• Genomics
• Oncology

Background:

• Cancer immunoediting describes the immune system's dual role in eliminating tumors and shaping their evolution.
• Genomic alterations resulting from immunoediting provide insights into tumor-immune interactions.

Purpose of the Study:

• To systematically evaluate and compare four distinct methods for quantifying cancer immunoediting.
• To assess the performance of these methods in colorectal cancer (CRC) and patient-derived xenografts (PDXs).

Main Methods:

• Systematic evaluation of four quantitative immunoediting methods.
• Analysis of The Cancer Genome Atlas (TCGA) colorectal cancer cohort.
• Comparison of 10 patient-derived xenografts (PDXs) with their matched primary tumors.

Main Results:

• The four methods identified 78.41%, 46.17%, 36.61%, and 4.92% of immunoedited CRC samples, collectively covering 92.90%.
• In PDX models, methods detected reduced immune selection (44.44%–60.0%), with combined methods identifying 77.78% of pairs.
• Observed-to-expected ratios were sensitive to neoantigen selection, unlike HLA-binding mutation ratio, immune dN/dS, and cancer cell fraction enrichment score.

Conclusions:

• Multiple immunoediting quantification methods are complementary and capture a significant proportion of immunoedited samples.
• Certain metrics (HLA-binding mutation ratio, immune dN/dS, enrichment score) show greater robustness against parameter variations.
• Integrating diverse methods is recommended for comprehensive future immunoediting analyses.