Abstract 80: Change in B cell lymphocyte expression from the pre- to post-malignant prostate predicts disease aggressiveness
Authors: Sadasivan Sudha M. , Chen Yalei , Gupta Nilesh S. , Sanii Ryan , Bobbitt Kevin R. , Chitale Dhananjay A. , Williamson Sean R. , Rundle Andrew G. , Tang Deliang , Rybicki Benjamin A. 
Published: April 2023

Abstract
Background: Inflammatory cells such as tumor infiltrating lymphocytes (comprising T and B cells) are often present in prostate tissue undergoing tumorigenesis but their role in disease progression is unclear. The current study aims to characterize the expression dynamics of CD3, CD4 and CD20 lymphocytes from the pre- to post-malignant prostate environment and the association of these dynamics with aggressive prostate cancer.
Methods: The study sample included 72 prostate cancer cases (44 whites and 28 African American) that underwent surgery as their primary treatment and had a benign prostate biopsy at least one year before diagnosis and were followed for biochemical recurrence (BCR). Counts of CD3-, CD4- and CD20-positive lymphocytes were quantified by immunohistochemistry using an automated multi-image processing procedure in pre-malignant benign biopsy (BB), tumor-adjacent benign (TAB) and malignant tumor glandular (MTG) regions of prostatectomy. A cox proportional hazards model was used to estimate the hazard ratio (HR) of time to BCR associated with inflammatory marker count in different regions of the prostate. Clustering was performed to identify similar trends of expression changes of CD3, CD4 and CD20 between the regions - BB, TAG and MTG using Time-series Anytime Density Peaks Clustering (TADPole).
Results: The risk of BCR was significantly reduced in men who had an elevated CD20 count in the TAG (HR=0.80, p=0.01) after adjusting for race, age at diagnosis, PSA at the time of benign biopsy and the Gleason grade group. CD3 and CD4 counts in the prostate regions did not show any significant association to BCR. TADPole identified four main different patterns of CD20 expression changes across the BB-TAB-MTG regions namely 1) minimal to no change in expression between the regions (n=45 pairs); 2) high expression in BB/no expression in TAG/higher expression in MTG (n=3 pairs); 3) high expression in BB/higher expression in TAG/no expression in MTG (n=8 pairs); 4) no expression in BB/higher expression in TAG compared to MTG (n=16 pairs). In comparison to the reference group (Cluster 1), Cluster 4 was at 3.5 times higher risk of BCR with an adjusted HR of 3.5 (p=0.0184).
Conclusion: Elevated CD20 expression in TAG was associated with less aggressive disease. Furthermore, cases that had CD20 expression highest in their benign prostate adjacent to tumor preceded by absence of CD20 expression in their pre-malignant benign prostate had the most aggressive disease course. Further studies are warranted to understand how CD20 lymphocyte dynamic changes influence prostate tumorigenesis.
Citation Format: Sudha M. Sadasivan, Yalei Chen, Nilesh S. Gupta, Ryan Sanii, Kevin R. Bobbitt, Dhananjay A. Chitale, Sean R. Williamson, Andrew G. Rundle, Deliang Tang, Benjamin A. Rybicki. Change in B cell lymphocyte expression from the pre- to post-malignant prostate predicts disease aggressiveness [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 80.