Urogenital Microbiota:Potentially Important Determinant of PD-L1 Expression in Male Patients with Non-muscle Invasive Bladder Cancer

Abstract

Background Urogenital microbiota may be associated with the recurrence of bladder cancer, but the underlying mechanism remains unclear. The notion that microbiota can upregulate PD-L1 expression in certain epithelial tumors to promote immune escape has been demonstrated. Thus, we hypothesized that the urogenital microbiota may be involved in the recurrence and progression of non-muscle invasive bladder cancer (NMIBC) by upregulating the PD-L1 expression. To test this hypothesis, we investigated the relationship between urogenital microbial community and PD-L1 expression in male patients with NMIBC. Results 16S rRNA gene sequencing was performed to analyse the composition of urogenital microbiota, and the expression of PD-L1 in cancerous tissues was detected by immunohistochemistry. The subjects (aged 43–79 years) were divided into PD-L1-positive group (Group P, n = 9) and PD-L1-negative group (Group N, n = 19) respectively based on their PD-L1 immunohistochemical results. No statistically significant differences were found in the demographic characteristics between group P and N. We observed that group P exhibited higher species richness (based on Observed species and Ace index, both P < 0.05). Furthermore, subgroup analysis showed that the increase in number of PD-L1 positive cells was accompanied by increased richness of urogenital microbiota. Significantly different composition of urogenital microbiota was found between group P and group N (based on weighted Unifrac and unweighted Unifrac distances metric, both P < 0.05). Enrichment of some bacterial genera (e.g., Leptotrichia, Roseomonas, and Propionibacterium) and decrease of some bacterial genera (e.g., Prevotella and Massilia) were observed in group P as compared with group N. These findings indicated that these genera may affect the expression of PD-L1 through some mechanisms to be studied. Conclusion Our study provided for the first time an overview of the association between urogenital microbiota and PD-L1 expression in male patients with NMIBC, indicating that urogenital microbiota was an important determinant of PD-L1 expression in male NMIBC patients.

Bladder Tissue Microbiome Composition in Patients of Bladder Cancer or Benign Prostatic Hyperplasia and Related Human Beta Defensin Levels

“…Thus, the higher amount of HBD2 induced by the bacteria present in the microbiome impairs the efficacy of BCG therapy [ 16 , 17 , 31 ]. Chen et al demonstrated a significant relationship between the amount of Leptotrichia , Roseomonas , Propionibacterium , Prevotella and Massilia genera in the microbiome of BC tissue and the PD-L1 expression of tumor cells [ 18 ]. Based on the experience of retrospective studies, it was found that the effectiveness of various checkpoint inhibitors was significantly reduced by different antibiotics when used in parallel; this effect may also be explained by distinct changes in microbial composition that are detrimental to therapeutic effectiveness of these anticancer medications [ 32 , 33 ].…”

“…Chang et al noted the detrimental effect of increased levels of HBD2 on BCG therapy against BC, and later confirmed the exact mechanism of action through Toll-like receptors [ 16 , 17 ]. It is well-known that not only the change in the gut microbiome affects the effectiveness of the anti-tumor checkpoint inhibitors, such as pembrolizumab or nivolumab, but the bacteria present in the urogenital system can also directly inhibit this therapy [ 18 ]. When planning individual therapies, it is essential to have more in-depth knowledge about the components of the bladder tumor microbiome and the HBD levels associated with them.…”

Bacteria for Treatment: Microbiome in Bladder Cancer

“…Researchers generally use urine samples and tissues to study bladder cancer. Despite stools being the most widely used material for other types of studies, urine and tissues are used the most for bladder cancer because of the location of the disease [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ].…”

“…Chen et al [ 43 ] conducted another trial. The authors sought to determine the relationship between PD-L1 expression and microbial abundance.…”

Antifungal immunity mediated by C-type lectin receptors may be a novel target in immunotherapy for urothelial bladder cancer

“…Recently, Chen et al. ( 103 ) explored for the first time the relationship between the microbiota profile and PD-L1 expression in patients with non-muscle-invasive bladder cancer. There were significant differences in the composition of specific bacteria genera between the PD-L1-high group and the PD-L1-low group.…”