Abstract 6670: Could immunotherapy offer potential in managing bacterial dysbiosis in prostate cancer

Abstract

Abstract Background: Since 2006 three studies, involving 289,089 adolescents, demonstrated a significant association (1.67(0.79-3.55),1.7(1.03-2.70),2.37(1.19-4.73)) between pubertal acne and poor outcome prostate cancer(PC) 30+ years later. This suggested Cutibacterium acnes, amicroaerophylic bacterium, might be contributing to PC bacterial dysbiosis analogous to the role of H. pylori in stomach cancer and explain why circumcision reduces PC risk. Six years ago, using MALDI-TOF, we demonstrated that the presence of seven obligate anaerobe species in addition to C. acnes were increased in PC and linked to increased PSA. This presentation studies stored samples from the PROVENT chemoprevention randomised PC active surveillance phase 2 trial analysed using 16S rDNA sequencing, and comparing obligate anaerobe frequency with those detected by culture and MALDI-TOF identification and their influence on PSA expression. Methods: 89 urines of PROVENT trial patients were studied using 16S rDNA sequencing and followed for 24 months. In addition, 39 previously reported MALDI-TOF screened cohort patients (21 PCs and 18 BPHs) followed for 43 months. The frequency of 7 obligate bacterial genera (Actinobaculum, Finegoldia, Prevotella, Peptoniphilus, Peptostreptococcus & Viellonella) was studied. Results: Twenty six of 89 (29%) PROVENT urine samples had a majority of bacteria detected as obligate anaerobes (mean=68%), while it was 12 of the 39 (31%) in PC tested in MALDI-TOF. In the combined series, those patients (n=38) with obligate anaerobes had mean PSA of 9.59 ug/L, while those without obligate anaerobes had a mean PSA of 6.29 ug/L (n=90), (t=-2.925, p = 0.0058). In the MALDI-TOF series, statistically increased urological intervention rate was associated with the presence of anaerobes (p=0.045, Fisher’s exact test). Discussion: These findings suggest that obligate anaerobe bacterial dysbiosis could be contributing to raised PSA through prostate cell damage, and possibly participating in the chronic inflammation and hypervascular changes that are seen in precancerous lesions. Checkpoint inhibitors have shown little benefit in prostate cancer. Recent reports from animal model studies of BCG resistance have suggested a short course combination of anti PDLI and anti NKG2a could break immune tolerance associated with expression of HLA-E and this approach could be of use to break tolerance to bacterial dysbiosis in the future. Citation Format: Tim Oliver, Belinda Nedjai, Emily Lane, Frank Chinegwundoh, Prabhakar Rajan, Jack Cuzick. Could immunotherapy offer potential in managing bacterial dysbiosis 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 6670.