Association of copy number alterations with the immune transcriptomic landscape in cancer

Tumors with high copy number alteration (CNA) burden often respond poorly to immune checkpoint inhibitor therapy. However, how CNAs affect the anti-cancer immune response remains unclear. To address this, we set out to capture the transcriptional effects of CNAs and define a comprehensive landscape of immune-related transcriptional patterns. Hereto, we applied consensus independent component analysis to 294,159 bulk transcriptomic profiles. We demonstrated the predictive power of these patterns for immunotherapy response, their reproducibility across platforms, and their applicability to bulk, single-cell, and spatial transcriptomic data. Our analysis identified both novel inverse and positive associations between high CNA burden and immune-related transcriptional patterns across various cancer types. For example, higher CNA burden correlated with increased immunosuppression, including IL-17-producing cells and regulatory T cells. This resource, along with the classification of these transcriptional patterns as immune-suppressive and immune-stimulatory, may provide insights to improve immunotherapy efficacy in tumors with high CNA burden.