Abstract 70: Unlocking the potential of the T-cell receptor in prostate cancer
Authors: Glud Eske Nøhr , Fredsøe Jacob H. , Nordentoft Iver K. , Kjær Asbjørn , Rusan Maria , Laursen Britt E. , Pedersen Bodil G. , Birkbark Nicolai J. , Dyrskjøt Lars , Borre Michael , Sørensen Karina Dalsgaard 
Published: March 2024

Abstract
Introduction: Prostate cancer (PC) is the most commonly diagnosed cancer among western men, with its diagnosis and subsequent monitoring still heavily dependent on the prostate specific antigen (PSA) test. However, the prognostic accuracy remains poor, leading to overtreatment of patients with non-aggressive cancer and undertreatment of those with aggressive cancer in need of intervention. Malignant cells are subject to constant monitoring and elimination by T-cell lymphocytes recognizing cancer-specific antigens through the T-cell receptor (TCR). Consequently, to establish itself and progress, cancer must evade or modulate the surveillance mechanisms of the immune system. As cancer growth accelerates, immune evasion becomes more difficult, resulting in a more pronounced impact on the immune system. Recently, our research group documented the clinical value of tumor-infiltrating T-cells as markers of aggressive PC. Here, we hypothesize that this signal can also be found in circulating T-cells isolated from the blood and used as proxy for the antitumoral immune response in tissue.
Methods: This study utilizes a diverse and well-characterized cohort, encompassing 220 castration resistant PC patients (CRPC) with blood samples taken at the time of CRPC diagnosis, 30 newly diagnosed hormone-naïve PC patients, and 30 healthy male donors. For a deeper understanding of the mechanisms underlying the antitumoral immune response and its impact on disease progression, a subset of CRPC patients (n = 25) are TCR sequenced throughout their disease course and uniquely, the TCR repertoire of their metastatic biopsies is characterized.
Results: In an initial comparison of 8 CRPC patients and 8 age-matched healthy males, we observed that cancer patients had a higher proportion of hyper-expanded T-cell clones (P = 0.003; Fisher’s exact test) and a less diverse TCR repertoire in blood. Furthermore, 86.5 % of hyper-expanded clones found in peripheral blood samples could also be found in malignant prostate tissue from matched CRPC patients, while overlap between patients was virtually non-existent
Conclusion: Our pilot study detected differences in the TCR repertoire between cancer patients and matched controls. The clones contributing most to this difference were concurrently found in malignant tissue indicating that the antitumoral immune response can indeed be detected in the periphery. Given these promising results, we are currently running the larger study described above to obtain a better understanding of the TCR repertoire and establish its prognostic potential in PC. While the findings showcased in this abstract exclusively stem from the pilot study, results for the full cohort will be presented at the conference.
Citation Format: Eske Nøhr Glud, Jacob H. Fredsøe, Iver K. Nordentoft, Asbjørn Kjær, Maria Rusan, Britt E. Laursen, Bodil G. Pedersen, Nicolai J. Birkbark, Lars Dyrskjøt, Michael Borre, Karina Dalsgaard Sørensen. Unlocking the potential of the T-cell receptor in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 70.