Tumor Fusion Burden as a Hallmark of Immune Infiltration in Prostate Cancer
Marie-Claire Wagle, Joseph Castillo, Shrividhya Srinivasan, Thomas Holcomb, Kobe Yuen, Edward E. Kadel, Sanjeev Mariathasan, Daniel L. Halligan, Adrian R. Carr, Max Bylesjö, Paul R. McAdam, Sarah Lynagh, Koen M. Marien, Mark Kockx, Yannick Waumans, Shih-Min A. Huang, Mark R. Lackner, Zineb Mounir
Abstract
have been characterized and linked to more aggressive disease. Individual tumor samples have been found to contain multiple fusions, and it remains unknown whether these fusions increase tumor immunogenicity. Here, we investigated the role of fusion burden on the prevalence and expression of key molecular and immune effectors in prostate cancer tissue specimens that represented the different stages of disease progression and androgen sensitivity, including hormone-sensitive and castration-resistant prostate cancer. We found that tumor fusion burden was inversely correlated with tumor mutational burden and not associated with disease stage. High fusion burden correlated with high immune infiltration, PD-L1 expression on immune cells, and immune signatures, representing activation of T cells and M1 macrophages. High fusion burden inversely correlated with immune-suppressive signatures. Our findings suggest that high tumor fusion burden may be a more appropriate biomarker than tumor mutational burden in prostate cancer, as it more closely associates with immunogenicity, and suggests that tumors with high fusion burden could be potential candidates for immunotherapeutic agents.