This $127,629 Project Grant award, which starts on February 1, 2025 and ends on January 31, 2027, is funded by the National Cancer Institute (NCI) through the Cancer Research Manpower (CFDA 93.398) program. The award supports research at the Harvard T.H. Chan School of Public Health to elucidate the role of germline and somatic human leukocyte antigen (HLA) variations in cellular immunity and the efficacy of immune checkpoint inhibitor (ICI) monotherapy for patients with non-small cell lung cancer (NSCLC). Specifically, the research aims to identify mechanisms linking HLA variations, somatic mutations, and immune phenotypes, examine how HLA variations impact ICI monotherapy outcomes, and develop interpretable machine learning models to predict ICI monotherapy progression-free and overall survival. This project leverages multi-omic data from over 80,000 NSCLC patients across several large cancer research consortia to advance precision medicine for this patient population.