Oral Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Novel diagnostic and prognostic biomarkers in prostate cancer (#19)

Jessica Da Gama Duarte 1 2 , Luke Quigley 1 2 , Leire Moya 3 , Louise Jackett 4 , Jyotsna Batra 3 , Andreas Behren 1 2 5
  1. Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia
  2. La Trobe University, School of Cancer Medicine, Heidelberg, VIC, Australia
  3. Translational Research Institute, Queensland University of Technology, Buranda, QLD, Australia
  4. Austin Health, Anatomical Pathology, Heidelberg, VIC, Australia
  5. Department of Medicine—Austin, University of Melbourne, Parkville, VIC , Australia

Prostate cancer remains one of the most prevalent cancers detected in males, yet current detection methods lack adequate specificity and sensitivity. While major improvements in screening have led to a reduction in advanced disease and mortality, patient overdiagnosis and overtreatment have, in turn, become problematic. Although most prostate tumours tend to be indolent, the high prevalence of the disease still results in a range of heterogeneous clinical outcomes. Many clinical and genetic factors have been explored for prognostic utility but only a few are routinely used. This emphasizes the need for novel diagnostic and prognostic biomarkers capable of effectively distinguishing healthy men from those with prostate cancer and effectively delineating indolent from aggressive disease.

Here, we screened serum samples from a retrospective cohort (n=110) of prostate cancer patients using a cancer array containing 123 tumour antigens, generating discrete antibody profiles for each patient. Downstream analyses were conducted to assess the efficacy of discovered tumour-associated antibodies as diagnostic and prognostic biomarkers using clinicopathological data. Findings inferred that combinations of unique antibodies could be used to detect prostate cancer with high sensitivity and specificity and aid in the prediction of disease outcome (i.e. relapse and survival). We also conducted multiplex immunohistochemistry on prostatectomy tissue samples from a subset of these patients (n=64) in order to investigate the role of tumour-infiltrating B cells. We found that abundant antibody-producing B cells and B cell aggregates were more prevalent in patients with high-grade disease and those with poor outcomes. Finally, our array-based diagnostic findings were validated using an external cohort (n=99) of prostate cancer patients.

In conclusion, the incorporation of circulating autoantibodies with current prostate cancer screening procedures has the potential to substantially improve prostate cancer diagnostics and prognostics, thereby reducing overdiagnoses and enabling informed therapeutic interventions. Moreover, tumour-infiltrating B cells may mediate pro-tumoural immunity.