膀胱癌（BCa）是一种严重影响患者生活质量和预后的疾病。为了解决这个问题，许多研究表明肠道微生物群调节肿瘤对治疗的反应。然而，这一点在膀胱癌中尚未得到充分表征。在这项研究中，我们的目的是确定肠道微生物群的多样性和组成或特定细菌属的密度是否影响膀胱癌患者的预后。我们收集了总共 50 名膀胱癌患者和 22 名匹配的非膀胱癌患者的粪便样本。 -对癌症个体进行 16S rDNA 测序，以研究副拟杆菌在这两组中的分布。此外，我们对癌症患者进行了随访，以了解不同属的微生物对患者生存的影响。我们对 Parabacteroides distasonis 进行了粪便微生物群移植 (FMT) 和单定植实验，以探索其对 MB49 荷瘤小鼠抗 PD-1 免疫治疗疗效的潜在增强作用。采用免疫组织化学、转录组学和分子实验分析来揭示其潜在机制。16S rDNA显示，与膀胱癌组相比，非癌症对照组中副拟杆菌属的丰度升高。肿瘤生长曲线结果表明，P. distasonis 和 ICI 治疗的联合治疗显着延迟了肿瘤生长，并增加了瘤内 CD4 T 和 CD8 T 细胞的密度。转录组分析结果表明，P. distasonis灌胃组中与抗肿瘤免疫反应相关的通路显着上调。 distasonis 递送联合 α-PD-1 mAb 可能是增强抗 PD-1 免疫治疗效果的新策略。这种效果可以通过激活免疫和抗肿瘤相关途径来实现。© 2024。作者。

Bladder cancer(BCa) was a disease that seriously affects patients' quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer.We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms.The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4+T and CD8+T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group.P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.© 2024. The Author(s).