Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Ann Surg Oncol. 2022 Apr;29(4):2495-2503. doi: 10.1245/s10434-021-11155-y. Epub 2022 Jan 9.
This study aims to reveal the clinical significance of stromal-infiltrating tumor-associated macrophages (TAMs) in muscle-invasive bladder cancer (MIBC).
This study included 288 patients from the TCGA database and 118 patients from Fudan University Shanghai Cancer Center with MIBC. The CIBERSORT model and immunohistochemistry were used to evaluate TAM infiltration. Cox regression analyses were employed to calculate their prognostic value.
Among all 23 immune phenotypes analyzed in the TCGA cohort, pan-macrophage infiltration was significantly associated with poor prognosis (p = 0.001). Further analyses found that stromal TAM infiltration could be an independent prognostic predictor for recurrence-free survival (RFS; HR: 1.019, 95% CI: 1.006-1.033, p = 0.004). High stromal infiltration was related to unfavorable RFS. After stratification by adjuvant chemotherapy (ACT), patients without ACT could be differentiated by TAM infiltration (p = 0.036), while patients with ACT could not. Moreover, TAM infiltration was negatively associated with IFN-γ-related mRNA panel, which was shown to have strong predictive value for clinical response to programmed death-1 (PD-1) inhibition.
Stromal TAM infiltration could be an independent prognosticator for MIBC patients. This might have potential to guide precise treatments such as ACT and immune checkpoint blockade in MIBC.
本研究旨在揭示肌层浸润性膀胱癌（MIBC）中肿瘤相关基质浸润性肿瘤相关巨噬细胞（TAMs）的临床意义。
本研究纳入了 TCGA 数据库中的 288 例 MIBC 患者和复旦大学上海癌症中心的 118 例 MIBC 患者。使用 CIBERSORT 模型和免疫组织化学方法评估 TAM 浸润。Cox 回归分析计算其预后价值。
在 TCGA 队列中分析的所有 23 种免疫表型中，泛巨噬细胞浸润与预后不良显著相关（p = 0.001）。进一步分析发现，基质 TAM 浸润可以作为无复发生存（RFS）的独立预后预测因子（HR：1.019，95%CI：1.006-1.033，p = 0.004）。高基质浸润与 RFS 不良相关。在辅助化疗（ACT）分层后，TAM 浸润可区分未接受 ACT 的患者（p = 0.036），而不能区分接受 ACT 的患者。此外，TAM 浸润与 IFN-γ 相关 mRNA 谱呈负相关，该谱对程序性死亡-1（PD-1）抑制的临床反应具有很强的预测价值。
基质 TAM 浸润可能是 MIBC 患者的独立预后标志物。这可能有助于指导 MIBC 的精确治疗，如 ACT 和免疫检查点阻断。
