Tumor-associated macrophages expressing galectin-9 identify immunoevasive subtype muscle-invasive bladder cancer with poor prognosis but favorable adjuvant chemotherapeutic response
Tumor-associated macrophages expressing galectin-9 identify immunoevasive subtype muscle-invasive bladder cancer with poor prognosis but favorable adjuvant chemotherapeutic response
复制标题
表达半乳糖凝集素 9 的肿瘤相关巨噬细胞识别免疫逃避亚型肌层浸润性膀胱癌，预后不良，但辅助化疗反应良好
DOI：
10.1007/s00262-019-02429-2
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发表时间：
2019-11-12
影响因子：
5.8
通讯作者：
Zhang, Weijuan
中科院分区：
文献类型：
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作者：
Qi, Yangyang;Chang, Yuan;Zhang, Weijuan
目的肿瘤相关巨噬细胞（TAMs）作为异质性亚群存在，在肿瘤免疫逃避中具有双重作用。本研究旨在评估半乳糖凝集素-9（+）肿瘤相关巨噬细胞（Gal-9（+）TAMs）在肌层浸润性膀胱癌（MIBC）中的临床作用。实验设计我们通过免疫组化（IHC）分析中山医院肿瘤微阵列（TMA）（n=141）和流式细胞术分析来自上海肿瘤中心的肿瘤标本（n=20）来鉴定Gal-9（+）TAMs。评估了该亚群中铂类化疗的生存获益。结果Gal-9（+）TAMs的表达频率随肿瘤分期、分级的升高而升高，随着肿瘤细胞增殖、分化程度的增加，Gal-9（+）TAMs的表达频率逐渐升高。Gal-9（+）TAM预测较差的总生存期（OS）和无复发生存期（RFS），并且在区分预后组方面优于Gal-9（-）TAM和TAM。在单因素和多因素考克斯回归分析中，Gal-9（+）TAM百分比高的患者在接受辅助化疗（ACT）后显示出显著的生存获益。高Gal-9（+）TAM浸润与调节性T细胞（TcB）和肥大细胞数量增加以及CD 8（+）T和树突状细胞（DCs）数量减少相关。Gal-9（+）TAM的密集浸润与细胞毒性分子减少、免疫检查点或免疫细胞表达的免疫抑制细胞因子增强以及肿瘤细胞的活跃增殖有关。结论Gal-9（+）TAM可预测MIBC患者的OS、RFS和ACT反应。高Gal-9（+）TAM与伴随T细胞耗竭的促肿瘤免疫环境相关。
Purpose Tumor-associated macrophages (TAMs) exist as heterogeneous subsets and have dichotomous roles in cancer-immune evasion. This study aims to assess the clinical effects of Galectin-9(+) tumor-associated macrophages (Gal-9(+)TAMs) in muscle-invasive bladder cancer (MIBC).Experimental design We identified Gal-9(+)TAMs by immunohistochemistry (IHC) analysis of a tumor microarray (TMA) (n=141) from the Zhongshan Hospital and by flow cytometric analysis of tumor specimens (n=20) from the Shanghai Cancer Center. The survival benefit of platinum-based chemotherapy in this subpopulation was evaluated. The effect of the tumor-immune microenvironment with different percentages of Gal-9(+)TAMs was explored.Results The frequency of Gal-9(+)TAMs increased with tumor stage and grade. Gal-9(+)TAMs predicted poor overall survival (OS) and recurrence-free survival (RFS) and were better than Gal-9(-)TAMs and TAMs to discriminate prognostic groups. In univariate and multivariate Cox regression analyses, patients with high percentages of Gal-9(+)TAMs showed the prominent survival benefit after receiving adjuvant chemotherapy (ACT). High Gal-9(+)TAM infiltration correlated with increasing numbers of regulatory T cells (Tregs) and mast cells and decreasing numbers of CD8(+)T and dendritic cells (DCs). Dense infiltration of Gal-9(+)TAMs was related to reduced cytotoxic molecules, enhanced immune checkpoints or immunosuppressive cytokines expressed by immune cells, as well as active proliferation of tumor cells. Additionally, the subpopulation accumulated was strongly associated with PD-1(+)TIM-3(+)CD8(+)T cells.Conclusions Gal-9(+)TAMs predicted OS and RFS and response to ACT in MIBC patients. High Gal-9(+)TAMs were associated with a pro-tumor immune contexture concomitant with T cell exhaustion.