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

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.

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

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Chunxiao Chen ◽  
Zehai Huang ◽  
Pengcheng Huang ◽  
Kun Li ◽  
Jiarong Zeng ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Immune Escape ◽  
Important Determinant ◽  
16S Rrna Gene Sequencing ◽  
Underlying Mechanism ◽  
Invasive Bladder Cancer ◽  
Rrna Gene ◽  
Muscle Invasive Bladder Cancer ◽  
Male Patients ◽  
Muscle Invasive

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.

scholarly journals Genomic Biomarkers and Underlying Mechanism of Benefit from BCG Immunotherapy in Non-Muscle Invasive Bladder Cancer

2020 ◽  
Vol 6 (2) ◽  
pp. 171-186
Author(s):  
Diogo A. Bastos ◽  
Romulo L. Mattedi ◽  
Rodrigo Barreiro ◽  
Filipe F. dos Santos ◽  
Vanessa Buzatto ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Underlying Mechanism ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Genomic Biomarkers ◽  
Bcg Immunotherapy ◽  
Muscle Invasive

Circulating tumor cell-driven use of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4523-4523
Author(s):  
Nick Beije ◽  
Ingeborg Elisabeth de Kruijff ◽  
Joep de Jong ◽  
Sjoerd O. Klaver ◽  
Peter de Vries ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Radical Surgery ◽  
High Rate ◽  
Invasive Bladder Cancer ◽  
Bladder Cancer Patient ◽  
Negative Group ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive ◽  
Related Mortality

4523 Background: International guidelines for the treatment of non-metastatic muscle-invasive bladder cancer (MIBC) recommend neoadjuvant chemotherapy (NAC), which, however, is underutilized in practice. We hypothesized that the absence of circulating tumour cells (CTCs), an established prognostic marker in MIBC, may identify patients with such a favourable prognosis that NAC may be withheld. Methods: The CirGuidance study included adults with clinical stage T2-T4aN0-N1M0 muscle-invasive urothelial carcinoma of the bladder who were fit to undergo radical cystectomy. CTCs were enumerated using the CellSearch system. CTC-negative patients (no CTCs detectable) underwent radical surgery without NAC; CTC-positive patients (≥1 detectable CTCs) were advised to receive NAC followed by radical surgery, but NAC could be withheld at the discretion of the treating physician. The primary endpoint was the two-year overall survival (OS) in the CTC-negative group, analysed in the intention-to-treat population. The prespecified criterion for trial success was a two-year OS of minimally 75% (95% confidence interval (CI) ±5%) in the CTC-negative group. Results: Of 315 patients screened for eligibility, 273 were enrolled in the study. The median age was 69 years; the median follow-up was 36 months. The two-year OS in the CTC-negative group was 69.5% (n = 203; 95% CI 62.6%-75.5%); in the CTC-positive group it was 58.2% (n = 70; 95% CI 45.5%-68.9%). CTC-positive patients had a higher rate of cancer-related mortality (hazard ratio (HR) 1.61, 95% CI 1.05-2.45, p = 0.03) and disease relapse (HR 1.87, 95% CI 1.28-2.73, p = 0.001) than CTC-negative patients. Explorative analyses suggested that CTC-positive patients who had received NAC (n = 22) survived longer than CTC-positive patients who had not (n = 48), with a two-year OS of 74.8% (95%CI 49.5%-88.8%) versus 52.0% (95% CI 37.2%-65.0%), respectively. Conclusions: The two-year OS in the CTC-negative group did not meet the prespecified criterion for trial success. However, given the trial population’s advanced age and high rate of non-cancer related mortality, the benefit of NAC is likely to be limited in CTC-negative MIBC patients. CTC enumeration at the moment of diagnosis could aid in the decision to prescribe neoadjuvant chemotherapy for a muscle-invasive bladder cancer patient as a criterion in addition to clinical characteristics. Clinical trial information: NL3954.

Sex and Racial Disparities in the Treatment and Outcomes of Muscle-invasive Bladder Cancer

Urology ◽  
2020 ◽  
Author(s):  
Jessica Marinaro ◽  
Alexander Zeymo ◽  
Jillian Egan ◽  
Filipe Carvalho ◽  
Ross Krasnow ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Racial Disparities ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive
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