RT Journal Article
SR Electronic
T1 Tumor Fusion Burden as a Hallmark of Immune Infiltration in Prostate Cancer
JF Cancer Immunology Research
JO Cancer Immunol Res
FD American Association for Cancer Research
SP 844
OP 850
DO 10.1158/2326-6066.CIR-19-0568
VO 8
IS 7
A1 Wagle, Marie-Claire
A1 Castillo, Joseph
A1 Srinivasan, Shrividhya
A1 Holcomb, Thomas
A1 Yuen, Kobe C.
A1 Kadel, Edward E.
A1 Mariathasan, Sanjeev
A1 Halligan, Daniel L.
A1 Carr, Adrian R.
A1 Bylesjo, Max
A1 McAdam, Paul R.
A1 Lynagh, Sarah
A1 Marien, Koen M.
A1 Kockx, Mark
A1 Waumans, Yannick
A1 Huang, Shih-Min A.
A1 Lackner, Mark R.
A1 Mounir, Zineb
YR 2020
UL http://cancerimmunolres.aacrjournals.org/content/8/7/844.abstract
AB Prostate cancer is the second leading cause of cancer-related death in men. Despite having a relatively lower tumor mutational burden than most tumor types, multiple gene fusions such as TMPRSS2:ERG 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.