CD25(+)FOXP3(+)CD45RA(-) 调节性 T 细胞浸润作为子宫内膜癌的预后生物标志物

英文原题：CD25(+)FOXP3(+)CD45RA(-) regulatory T-cell infiltration as a prognostic biomarker for endometrial carcinoma.

PubMed 2024/09/04（内容时间） BMC Cancer Q2 · IF 4.1（JCR 2025）

研究概要

目前的观察提示，CD25+或CD25+FOXP3+CD45RA-细胞与CD8+细胞之间的平衡，对应促进或抑制肿瘤血管生成的作用，影响肿瘤化疗敏感性，从而具有预后意义。CD25+FOXP3+CD45RA-效应性Treg肿瘤浸润可作为有用的预后生物标志物，并可能成为通过新型治疗手段对晚期/复发性子宫内膜癌进行肿瘤化疗敏感性免疫治疗干预的潜在靶点。

研究思路结论见上方概要

背景

据报道，调节性T（Treg）细胞在肿瘤血管生成以及抗肿瘤免疫中发挥关键作用。为了探索其治疗潜力，我们研究了Treg标志物在子宫内膜癌中的精确预后影响。

方法

我们对176例连续在本机构接受治疗的子宫内膜癌原发肿瘤标本进行了CD25、FOXP3、CTLA4和CD45RA的多重免疫荧光及定量图像分析。进一步开展生物信息学分析以佐证这些发现。

结果

高 CD25+、FOXP3+ 和 CD25+FOXP3+CD45RA- 基质细胞计数与更好的总生存期（OS）相关（p = 0.00019、0.028 和 0.0012），并与 MSI-high 相关（p = 0.015、0.016 和 0.047）。高 CD45RA+ 基质细胞计数与浅肌层浸润相关（p = 0.0038）。通过 Kaplan-Meier plotter 进行的生物信息学生存分析显示，高 CD25、FOXP3、CTLA4 和 CD45RA mRNA 表达与更好的 OS 相关（p = 0.046、0.00042、0.000044 和 0.0022）。对多种临床病理预后因素进行的单因素和多因素分析表明，高 CD25+ 或 CD25+FOXP3+CD45RA- 基质细胞计数对有利 OS 具有显著且独立的意义（p = 0.0053 和 0.0015）。我们随后分析了复发病例中多重免疫荧光结果与初次化疗后无治疗间期（TFI）之间的相关性，未发现显著关联。进一步分析显示，高 CD25+：CD8+ 细胞计数比值或 CD25+FOXP3+CD45RA-：CD8+ 细胞计数比值与更长的 TFI 相关（p = 0.021 和 0.021）。

展开英文摘要原文

BACKGROUND: Regulatory T (Treg) cells reportedly play crucial roles in tumor angiogenesis as well as antitumor immunity. In order to explore their therapeutic potential, we investigated the precise prognostic impact of Treg markers in endometrial carcinoma. METHODS: We performed multiplexed immunofluorescence and quantitative image analyses of CD25, FOXP3, CTLA4, and CD45RA in tumor specimens from 176 consecutive patients treated at our institution for primary endometrial carcinomas. Bioinformatics analyses were further conducted to corroborate the findings. RESULTS: High CD25 + , FOXP3 + , and CD25 + FOXP3 + CD45RA - stromal cell counts correlated with better overall survival (OS) (p = 0.00019, 0.028 and 0.0012) and MSI-high (p = 0.015, 0.016 and 0.047). High CD45RA + stromal cell count was associated with superficial myometrial invasion (p = 0.0038). Bioinformatics survival analysis by Kaplan-Meier plotter showed that high CD25, FOXP3, CTLA4, and CD45RA mRNA expressions correlated with better OS (p = 0.046, 0.00042, 0.000044, and 0.0022). Univariate and multivariate analyses with various clinicopathologic prognostic factors indicated that high CD25 + or CD25 + FOXP3 + CD45RA - stromal cell count was significant and independent for favorable OS (p = 0.0053 and 0.0015). We subsequently analyzed the correlations between the multiplexed immunofluorescence results and treatment-free interval (TFI) after primary chemotherapy in recurrent cases, finding no significant associations. Further analysis revealed that high ratio of CD25 + : CD8 + cell count or CD25 + FOXP3 + CD45RA - : CD8 + cell count correlated with longer TFI (p = 0.021 and 0.021). CONCLUSION: The current observations suggest that the balance between CD25 + or CD25 + FOXP3 + CD45RA - cells and CD8 + cells, corresponding to promoting or inhibiting effect on tumor angiogenesis, affect tumor chemosensitivity leading to prognostic significance. CD25 + FOXP3 + CD45RA - effector Treg tumor infiltration may serve as a useful prognostic biomarker and a potential target for immunotherapeutic manipulation of tumor chemosensitivity by novel management for advanced/recurrent endometrial carcinomas.

论文信息

作者: Suto A、Minaguchi T、Qi N、Fujieda K、Itagaki H、Tenjimbayashi Y、Shikama A、Tasaka N
第一作者单位: Department of Obstetrics and Gynecology, Institute of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, 305-8575, Ibaraki, Japan.Japan
通讯作者单位: Department of Obstetrics and Gynecology, Institute of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, 305-8575, Ibaraki, Japan. minaguchit@md.tsukuba.ac.jp.Japan
期刊: BMC cancer2024 Sep 4

原文标识: PubMed 39232704　·　DOI 10.1186/s12885-024-12851-0

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