Department of Urology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China,
Institute of Urology, Surgical Research Center, Southeast University Medical School, Nanjing, China,
Urol Int. 2023;107(1):58-63. doi: 10.1159/000519129. Epub 2021 Oct 27.
Cisplatin-containing combination chemotherapy has been the standard of care since the late 1980s, but the response rate is <50%. Studies have shown that the efficiency of chemotherapy differs among molecular subtypes of bladder cancer. In this study, we aimed to correlate FOXA1, a marker for differentiation of the basal and luminal subtypes, with tumor immune cell infiltration and the effect of chemotherapy in bladder cancer.
Eighty-three patients with bladder cancer treated with chemotherapy were reviewed. Clinicopathological variables for each case were recorded. FOXA1, M2 tumor-associated macrophage (TAM), dendritic cell (DC), and cytotoxic T lymphocyte (CTL) were examined by immunohistochemistry. The relationship between FOXA1, immune cell infiltration, and clinical response to chemotherapy was assessed.
The overall objective response rate was 34%. The objective response rate for tumors with lower FOXA1 expression was 58% and for tumors with higher FOXA1 expression was 12%. Tumors with infiltrated M2 TAM proportion <3% had a higher objective response rate compared with infiltrated M2 TAM proportion >3% tumors (46% vs. 21%, p = 0.02). Tumors with infiltrated CTL proportion >5% had a higher objective response rate compared with infiltrated CTL proportion <5% tumors (50% vs. 17%, p = 0.002). DCs showed no significant differences. We found that the objective response rate for tumors with lower FOXA1 expression, proportion <3% M2 TAM infiltration, and proportion >5% CTL infiltration is 82%. Lower FOXA1 expression was associated with low M2 TAM infiltration and high CTL infiltration.
Thus, we showed that in patients with bladder cancer who received chemotherapy, the higher clinical response rate is associated with low FOXA1 expression, low M2 TAM infiltration, and high CTL infiltration.
自 20 世纪 80 年代末以来，含顺铂的联合化疗一直是标准治疗方法，但反应率<50%。研究表明，膀胱癌的分子亚型不同，化疗的效率也不同。在这项研究中，我们旨在将 FOXA1 与肿瘤免疫细胞浸润和膀胱癌化疗效果相关联，FOXA1 是基底和腔亚型分化的标志物。
对 83 例接受化疗的膀胱癌患者进行了回顾性研究。记录了每个病例的临床病理变量。通过免疫组织化学检查 FOXA1、M2 肿瘤相关巨噬细胞（TAM）、树突状细胞（DC）和细胞毒性 T 淋巴细胞（CTL）。评估 FOXA1、免疫细胞浸润与化疗临床反应之间的关系。
总体客观缓解率为 34%。FOXA1 表达较低的肿瘤客观缓解率为 58%，FOXA1 表达较高的肿瘤客观缓解率为 12%。浸润 M2 TAM 比例<3%的肿瘤客观缓解率高于浸润 M2 TAM 比例>3%的肿瘤（46%比 21%，p=0.02）。浸润 CTL 比例>5%的肿瘤客观缓解率高于浸润 CTL 比例<5%的肿瘤（50%比 17%，p=0.002）。DC 无显著差异。我们发现，FOXA1 表达较低、M2 TAM 浸润比例<3%、CTL 浸润比例>5%的肿瘤客观缓解率为 82%。FOXA1 表达较低与低 M2 TAM 浸润和高 CTL 浸润相关。
因此，我们表明，在接受化疗的膀胱癌患者中，较高的临床缓解率与 FOXA1 表达降低、M2 TAM 浸润减少和 CTL 浸润增加相关。
