Expression of FOXA1 Is Associated with the Tumor-Infiltrating M2 Macrophage, Cytotoxic T Lymphocyte, and Effect of Chemotherapy in Bladder Cancer.

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.

Urologia internationalis. 2021 Oct 27 [Epub ahead of print]

Yiduo Wang, Huan Qu, Bin Xu, Jianping Wu, Kai Lu, Chunhui Liu, Shuqiu Chen, Ming Chen

Department of Urology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China, ., Health Management Center, Zhongda Hospital, Southeast University, Nanjing, China., Department of Urology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.

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