Systematic integration of machine learning algorithms to develop immune escape-related signatures to improve clinical outcomes in lung adenocarcinoma patients.

Abstract

Immune escape has recently emerged as one of the barriers to the efficacy of immunotherapy in lung adenocarcinoma (LUAD). However, the clinical significance and function of immune escape markers in LUAD have largely not been clarified. In this study, we constructed a stable and accurate immune escape score (IERS) by systematically integrating 10 machine learning algorithms. We further investigated the clinical significance, functional status, TME interactions, and genomic alterations of different IERS subtypes to explore potential mechanisms. In addition, we validated the most important variable in the model through cellular experiments. The IERS is an independent risk factor for overall survival, superior to traditional clinical variables and published molecular signatures. IERS-based risk stratification can be well applied to LUAD patients. In addition, high IERS is associated with stronger tumor proliferation and immunosuppression. Low IERS exhibited abundant lymphocyte infiltration and active immune activity. Finally, high IERS is more sensitive to first-line chemotherapy for LUAD, while low IERS is more sensitive to immunotherapy. In conclusion, IERS may serve as a promising clinical tool to improve risk stratification and clinical management of individual LUAD patients and may enhance the understanding of immune escape.