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NEO2IS_ITHS

A novel integrated approach to predicting cancer immunotherapy efficacy

Somatic mutations and structural variants were detected using WES and RNA-seq data. Translated proteins were chopped into 8-11 kmers peptides encompassing the mutated residues (for SNVs and indels) and fusion breakpoint (for fusions) until a stop codon. Mutated peptides with binding affinity <0.5 % Rank determined by NetMHCpan were considered as candidate neoantigens. The neoantigen load score was calculated based on outputs of deepHLApan.

We developed a composite score (NEO2IS) to characterize interplays between cancer and CD8+ T-cell subpopulations (dominantly exhausted CD8+ T-cells). NEO2IS improved prediction accuracy of patient responses to immune-checkpoint blockades (ICBs). We found that TCR repertoire diversity was consistent with the neoantigen heterogeneity under evolutionary selections. Our defined neoantigen heterogeneity score (NEOITHS) delineated infiltration degree of CD8+ T lymphocytes with different differentiation states and manifested the impact of negative selection pressure on CD8+ T-cell lineage heterogeneity or tumor ecosystem plasticity. We further classified included tumors into four distinct immune subtypes, and examined how neoantigen-T cells interactions affected disease progression and response to treatment.

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luoruihan@stu.cqmu.edu.cn

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