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

Abstract

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.

Keywords

• Bladder cancer
• Urogenital tract
• Microbiota
• PD-L1
• Immune escape