Abstract The identification of biomarkers that predict patient response to immune checkpoint blockade (ICB) is a key focus of current cancer research. We and others have found that high levels of Somatic Copy Number Alterations (SCNAs) in tumors are associated with decreased infiltration by cytotoxic immune cells and predict patient’s response to ICB. Recently, we predicted that the strongest SCNA driver of cytotoxic T cell depletion in HPV-negative oral cancer, was the loss of the entire 9p arm and that it was a marker of poor survival in recurrent oral cancers treated by anti-PD1 therapy. 9p arm loss is among the most common SCNAs in solid tumors and we revealed its importance beyond 9p21.3 deletion (i.e., CDKN2A and the IFNA cluster).To systematically investigate the immune-related role of 9p deletion and other SCNAs in cancer, we have developed a computational pipeline to identify the genes altered by SCNAs predicting the strongest risk of cancer immune evasion. We analyzed 7 solid tumor types and identified thousands of tumor-specific SCNAs predicting an immune cold phenotype but only ~100 SCNAs were conserved across all tumor types. Strikingly, 60% of the conserved deletions were localized on the 9p arm and the strongest 9p candidates included some known cancer drivers but also new candidates such as RANBP6 and TOPORS, that have been suggested to decrease proinflammatory and pro-immunogenic molecules. We have identified a 17-gene cluster deletion in 9p13 composed mostly of genes involved in proteasomal degradation or membrane trafficking, suggesting that its deletion might disturb MHC-mediated antigen presentation. We are now engineering human and mouse oral cancer cell lines to recapitulate 9p deletion and decipher its role in immune evasion through in vitro and in vivo immunological assays. We are also using the parameters we determined in our computational pipeline to develop a machine learning method improving our prediction of SCNAs driving immune evasion. Our findings identified 9p deletion as a novel biomarker for predicting clinical benefit of ICB and will allow a better understanding of the SCNA-mediated mechanisms suppressing tumor immune response. Citation Format: Joy Bianchi. 9p arm loss is an important predictor of immune evasion in several human cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB354.