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.

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Profiling the Urinary Microbiota in Men with Positive versus Negative PD-L1 Expression for Non-muscle Invasive Bladder Cancer

10.21203/rs.3.rs-745184/v1 ◽

2021 ◽

Author(s):

Chunxiao Chen ◽

Zehai Huang ◽

Pengcheng Huang ◽

Kun Li ◽

Jiarong Zeng ◽

...

Keyword(s):

Bladder Cancer ◽

Immune Escape ◽

Underlying Mechanism ◽

Invasive Bladder Cancer ◽

Negative Group ◽

Muscle Invasive Bladder Cancer ◽

Unweighted Unifrac ◽

Male Patients ◽

Urinary Microbiota ◽

Muscle Invasive

Abstract Background Urinary microbiota is associated with the recurrence of bladder cancer, but the underlying mechanism remains unclear. The notion that microbiota can upregulate PD-L1 expression in tumors to promote immune escape have been demonstrated. We hypothesized that the urinary microbiota may be involved in the recurrence and progression of non-muscle invasive bladder cancer (NMIBC) by upregulating the PD-L1 expression. For proving this hypothesis, we firstly performed this study to characterize the potential urinary microbial community possibly associated with PD-L1 expression in male patients with NMIBC. Results The subjects (aged 43–79 years) based on their PD-L1 immunohistochemical results were divided into PD-L1-positive group (P group) and PD-L1-negative group (N group) respectively. We observed that P group exhibited higher species richness and diversity (based on Observed species and Ace index, both P < 0.05). Significantly different composition of urinary microbiota was found between P group and N group (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 P group as compared with N group. These findings indicate that these genera may affect the expression of PD-L1 through some mechanisms to be studied. PICRUSt analysis showed that several pathways involved in the metabolism of chemical compounds and immune-related disease were enriched in the PD-L1 negative group. Conclusion Our data indicate that urinary microbiota may be an important determinant of PD-L1 expression in male NMIBC patients. The findings of our study may facilitate subsequent study on the role and mechanism of urinary microbiota in the recurrence of NMIBC and may also pave a new way for the better application of PD1 or PD-L1 blockers in bladder cancer in the future.

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