非常规 T 细胞在泌尿系统肿瘤中：能抓住就抓住
Unconventional T cells in urological cancers: catch them if you can.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
MS4A4A 阳性肿瘤相关巨噬细胞与膀胱尿路上皮癌患者的不良预后和 T 细胞耗竭相关
英文原题：MS4A4A-positive tumor-associated macrophages associate with poor prognosis and T-cell exhaustion in patients with urothelial carcinoma of the bladder.
查看英文原题
MS4A4A-positive tumor-associated macrophages associate with poor prognosis and T-cell exhaustion in patients with urothelial carcinoma of the bladder.
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中文摘要
肿瘤相关巨噬细胞（TAM）在癌症中具有多种强效功能，是重要的治疗靶点。MS4A4A是一种功能性TAM标志物，但其预后意义尚有争议。
本研究旨在评估膀胱尿路上皮癌（UCB）中MS4A4A⁺ TAM浸润与临床结局之间的关系及其对免疫图谱的影响。研究分析了中山大学孙逸仙纪念医院队列中的400例UCB患者。采用免疫组化定量MS4A4A⁺ TAM，并评估其空间分布及多种免疫成分，同时分析卡介苗（BCG）免疫治疗获益和生存结局。
此外，还检查了同一患者复发或进展前后的配对UCB组织。研究发现，与肿瘤内区域相比，间质区域MS4A4A⁺ TAM水平更高；在这两个区域中，其水平升高均与肿瘤分期较晚和预后较差相关。同一患者复发/进展前后MS4A4A⁺ TAM数量无显著差异。间质MS4A4A⁺ TAM与BCG疗效和无复发生存期呈负相关。这些TAM在相应区域内与CD8⁺ T细胞、Foxp3⁺调节性T细胞、免疫检查点（PD-1、LAG-3、HAVcr-2、TIGIT）及抗炎分子（TGF-β1、IL-4）呈正相关。
此外，UCB组织中的MS4A4A⁺ TAM高表达TGF-β1和HAVcr-2。体外实验中，IL-4诱导小鼠骨髓来源巨噬细胞表达MS4A4A；敲低Ms4a4a则降低抗炎分子Arg1表达并提高促炎分子Nos2表达。这些发现表明，MS4A4A是UCB可靠的预后标志物和BCG应答预测因子，凸显其在塑造免疫图谱和免疫治疗结局中的作用。
展开英文摘要原文
Tumor-associated macrophages (TAMs) have multiple potent functions in cancer representing important therapeutic targets. MS4A4A is a functional TAM marker with controversial implications for prognosis.
This study aimed to evaluate the association between MS4A4A + TAM infiltration and clinical outcomes in urothelial carcinoma of the bladder (UCB), as well as their impact on the immune landscape. A total of 400 UCB patients from cohorts at Sun Yat-sen Memorial Hospital were analyzed. Immunohistochemistry was used to quantify MS4A4A + TAMs and assess their spatial distribution alongside various immune components, evaluate the benefit of Bacillus Calmette-Guérin (BCG) immunotherapy, and analyze survival outcomes.
Additionally, matched UCB tissues were examined before and after recurrence or progression.
We observed that MS4A4A + TAMs were present at higher levels in the stromal region compared to the intratumoral region, and correlated with advanced tumor stage and poor prognosis in both regions. No significant difference was observed in the number of MS4A4A + TAMs before and after recurrence/progression in the same patient.
Stromal MS4A4A + TAMs were negatively correlated with BCG efficacy and recurrence-free survival. These TAMs were positively associated with CD8 + T cells, Foxp3 + regulatory T cells, immune checkpoints (PD-1, LAG-3, HAVcr-2, TIGIT), and anti-inflammatory molecules (TGF-β1, IL-4) in the same respective regions.
Additionally, MS4A4A + TAMs expressed high levels of TGF-β1 and HAVcr-2 in UCB tissues. In vitro, IL-4 induced MS4A4A expression in mouse bone marrow-derived macrophages, while Ms4a4a knockdown reduced the anti-inflammatory molecule Arg1 and increased pro-inflammatory molecule Nos2 expression.
These findings demonstrate that MS4A4A is a reliable prognostic marker and predictor of BCG response in UCB, highlighting its role in shaping the immune landscape and immunotherapy outcomes. © 2025 The Pathological Society of Great Britain and Ireland.
论文信息
- 作者
- Yang T、Sun X、Chen J、Li J、Liu C、Yu J、Meng W、Wang Y
- 单位
- Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, PR China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- The Journal of pathology2025 Oct
- 原文标识
- PubMed 40804697 · DOI 10.1002/path.6465