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卵黄囊瘤中 PD-1/PD-L1 和 CTLA4 表达及 TIL(肿瘤浸润淋巴细胞)的详细特征分析

英文原题:Detailed characterization of PD-1/PD-L1 and CTLA4 expression and tumor-infiltrating lymphocytes in yolk sac tumors.

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Detailed characterization of PD-1/PD-L1 and CTLA4 expression and tumor-infiltrating lymphocytes in yolk sac tumors.

PubMed 2023/07/13(内容时间) Hum Immunol Q4 · IF 2.1(JCR 2025)

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研究概要

YSTs 中 CTLA4 表达频率高,PD-1/PD-L1 表达、免疫炎症表型和 TLSs 频率低,但睾丸中的 YSTs 显示出更高的 TILs 密度和更高的免疫检查点分子表达。

研究思路结论见上方概要

免疫检查点阻断(ICB)被认为是癌症治疗的一种有前景的方法。然而,ICB 疗法在卵黄囊瘤(YSTs)中的效力尚未得到证实,肿瘤免疫微环境的综合分析以及 PD-1/PD-L1 和 CTLA4 的表达也尚未得到全面评估。

对23例YSTs患者的福尔马林固定、石蜡包埋肿瘤标本进行免疫组化检测,以检测肿瘤浸润T细胞的密度和分布、三级淋巴结构(TLSs),以及PD-1/PD-L1和CTLA4的表达。

总体而言,超过半数(61%)的患者基于CD3+ T细胞表现出免疫荒漠表型。在五个肿瘤样本(21.7%)中检测到PD-1表达,而PD-L1表达在肿瘤细胞(TCs)和TIL(肿瘤浸润淋巴细胞)(TILs)中呈现不同的阳性率(39.1%和17.4%)。值得注意的是,CTLA4在TCs和TILs中的阳性表达率(69.6%和56.5%)显著高于PD-1和PD-L1的表达率。此外,在21.74%的所有组织中观察到TLSs,且具有TLSs的样本表现出显著更高的TILs密度和更高的免疫检查点分子表达,尤其是PD-1/PD-L1。另外,位于睾丸的肿瘤也表现出更高的TILs密度和更高的免疫检查点分子表达。

展开英文摘要原文

Immune checkpoint blockade (ICB) is considered as a promising approach for cancer treatment. However, the potency of ICB therapy in yolk sac tumors (YSTs) has not been confirmed, and the comprehensive analysis of tumor immune microenvironment and the expression of PD-1/PD-L1 and CTLA4 were also not thoroughly evaluated.

Immunohistochemistry was performed in formalin-fixed, paraffin-embedded tumor specimens from 23 YSTs patients to detect the density and distribution of tumor-infiltrating T cells, tertiary lymphoid structures (TLSs), as well as the expression of PD-1/PD-L1 and CTLA4.

Overall, more than half (61 %) of all patients exhibited an immune-desert phenotype based on CD3 + T cells. PD-1 expression was identified in five tumor samples (21.7 %), and PD-L1 expression exhibited a different positive rate in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) (39.1 % and 17.4 %). Noteworthily, the rate of positive CTLA4 expression in both TCs and TILs was markedly higher (69.6 % and 56.5 %) than those of PD-1 and PD-L1 expression. Furthermore, TLSs were observed in 21.74 % of all tissues, and samples with TLSs exhibited significantly higher densities of TILs and higher expression of immune checkpoint molecules, particularly PD-1/PD-L1. In addition, tumors located in testes also exhibited a higher density of TILs and higher expression of immune checkpoint molecules.

Generally a high frequency of CTLA4 expression was found, PD-1/PD-L1 expression, the immune-inflamed phenotype, and TLSs were low frequency in YSTs, however, YSTs in testes showed a higher density of TILs and higher expression of immune checkpoint molecules.

论文信息

作者
Zhang D、Xu H、Zhao C、Qin L、Wei R、Xi L、Li F
第一作者单位
Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Department of Gynecologic Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.China
通讯作者单位
Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Department of Gynecologic Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address: lifeianhui@163.com.China
期刊
Human immunology2023 Oct
原文标识
PubMed 37453913 · DOI 10.1016/j.humimm.2023.07.003