← 返回前沿论文

肿瘤相关巨噬细胞的空间免疫表型分析预测透明细胞肾细胞癌的预后结局

英文原题:Spatial immunophenotyping of tumor-associated macrophages predicts prognostic outcomes in clear cell renal cell carcinoma.

查看英文原题

Spatial immunophenotyping of tumor-associated macrophages predicts prognostic outcomes in clear cell renal cell carcinoma.

PubMed 2026/02/27(内容时间) Urol Oncol Q2 · IF 2.8(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

研究概要

ccRCC 中 TAM 的不同表型和空间分布与预后结局相关。中央型 M2 样 TAM 与不良结局相关,而中央型 M1 样 TAM 与良好预后相关。TIL 未显示出独立的预后价值。

研究思路结论见上方概要

透明细胞肾细胞癌(ccRCC)是最常见的肾癌亚型,具有高转移率和高复发率。其肿瘤微环境(TME),尤其是肿瘤相关巨噬细胞(TAMs)和TIL(肿瘤浸润淋巴细胞)(TILs),影响免疫逃逸和肿瘤进展。本研究基于TAM和TIL亚群的表型及其在TME中的空间分布,评估了其预后意义。

本回顾性研究纳入2011年至2013年间在Asan Medical Center接受手术的643例ccRCC患者。对来自肿瘤中央和外周区域的组织芯片进行多重免疫荧光染色。使用自动成像软件定量M1/M2巨噬细胞和T细胞标志物,并使用最大选择秩统计量定义最佳截断值,同时进行额外的敏感性分析以评估稳健性。采用Cox回归评估生存结局,组间比较使用适当的统计检验。

M2样TAMs(CD68+CD206+)高中央密度与较差的总生存期、无转移生存和无进展生存期(PFS)相关(P < 0.05)。相反,M1样TAMs(CD68+iNOS+)高中央密度与较好的PFS相关(P = 0.034)。在所有肿瘤区域,M2样TAMs均比M1样更丰富。外周CD3+ TILs比中央更常见。探索性分析显示,免疫细胞密度与酪氨酸激酶抑制剂治疗反应之间相关性较弱。

展开英文摘要原文

This retrospective study included 643 ccRCC patients who underwent surgery at Asan Medical Center between 2011 and 2013. Multiplex immunofluorescence staining was performed on tissue microarrays from central and peripheral tumor regions. Markers for M1/M2 macrophages and T cells were quantified using automated imaging software, and optimal cutoffs were defined using maximally selected rank statistics, with additional sensitivity analyses performed to assess robustness. Survival outcomes were assessed with Cox regression, and group comparisons used appropriate statistical tests.

High central density of M2-like TAMs (CD68+CD206+) was associated with poor overall, metastasis-free, and progression-free survival (PFS) (P < 0.05). In contrast, high central density of M1-like TAMs (CD68+iNOS+) was associated with favorable PFS (P = 0.034). M2-like TAMs were more abundant than M1-like across all tumor regions. Peripheral CD3+ TILs were more frequent than in the center. Exploratory analyses showed weak correlations between immune cell densities and response to tyrosine kinase inhibitor therapy.

Distinct phenotypes and spatial distributions of TAMs were associated with prognostic outcomes in ccRCC. Central M2-like TAMs were associated with poor outcomes, while central M1-like TAMs were linked to favorable prognosis. TILs did not demonstrate independent prognostic value.

论文信息

作者
Uh J、Kim J、Shin SJ、Ko J、Go H
第一作者单位
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.South Korea
通讯作者单位
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: damul37@amc.seoul.kr.South Korea
期刊
Urologic oncology2026 May
原文标识
PubMed 41759396 · DOI 10.1016/j.urolonc.2026.111038