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TIM-3 可作为高危软组织肉瘤(HR-STS)特定患者亚群中的潜在免疫治疗靶点

英文原题:TIM-3 Qualifies as a Potential Immunotherapeutic Target in Specific Subsets of Patients with High-Risk Soft Tissue Sarcomas (HR-STS).

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TIM-3 Qualifies as a Potential Immunotherapeutic Target in Specific Subsets of Patients with High-Risk Soft Tissue Sarcomas (HR-STS).

PubMed 2023/05/12(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

(1) 背景:T细胞免疫球蛋白和黏蛋白结构域包含蛋白3(TIM-3)是一种T细胞上的免疫检查点受体,其表达与多种实体瘤的不良预后和晚期肿瘤分期相关。目前正在多项临床试验中研究TIM-3的阻断治疗。

本研究探讨TIM-3在高危软组织肉瘤(HR-STS)中的表达。(2) 方法:在HR-STS患者的治疗前活检组织中,分析肿瘤细胞TIM-3的蛋白水平表达。将TIM-3表达与HR-STS患者的临床病理参数进行相关性分析,包括TIL(肿瘤浸润淋巴细胞)计数、程序性细胞死亡1(PD-1)和程序性细胞死亡配体1(PD-L1)表达。分析TIM-3表达对生存的影响。(3) 结果:在179例HR-STS患者的治疗前活检组织中,101例(56%)观察到TIM-3表达。与其他组织学亚型相比,未分化多形性肉瘤(UPS)中TIM-3表达显著更常见(p < 0.001),且与高TIL计数(p < 0.001)、高PD-1(p < 0.001)和高PD-L1表达(p < 0.001)显著相关。TIM-3表达对HR-STS患者的生存无预后影响。(4) 结论:这是首项证实在HR-STS特定患者亚群中肿瘤细胞显著表达TIM-3的研究。TIM-3有望成为HR-STS的潜在免疫治疗靶点。

展开英文摘要原文

(1) Background: The expression of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), an immune checkpoint receptor on T cells, has been associated with dismal outcomes and advanced tumor stages in various solid tumors. The blockade of TIM-3 is currently under examination in several clinical trials.

This study examines TIM-3 expression in high-risk soft tissue sarcomas (HR-STS). (2) Methods: Tumor cell expression of TIM-3 on protein level was analyzed in pre-treatment biopsies of patients with HR-STS. TIM-3 expression was correlated with clinicopathological parameters including tumor-infiltrating lymphocyte (TIL) counts, programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PDL-1) expression in patients with HR-STS. Survival dependent on the expression of TIM-3 was analyzed. (3) Results: TIM-3 expression was observed in 101 (56%) out of 179 pre-treatment biopsies of patients with HR-STS.

TIM-3 expression was significantly more often observed in undifferentiated pleomorphic sarcomas (UPS) compared to other histological subtypes ( p < 0. 001), high TIL counts ( p < 0. 001), and high PD-1 ( p < 0. 001) and PD-L1 expression ( p < 0. 001). TIM-3 expression did not have a prognostic impact on survival in patients with HR-STS. (4) Conclusions: This is the first study to demonstrate a significant tumor cell expression of TIM-3 in specific subsets of patients with HR-STS. TIM-3 qualifies as a potential immunotherapeutic target in HR-STS.

论文信息

作者
Berclaz LM、Altendorf-Hofmann A、Lindner LH、Burkhard-Meier A、Di Gioia D、Dürr HR、Klein A、Albertsmeier M
第一作者单位
Department of Internal Medicine III, University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany.Germany
通讯作者单位
Institute of Pathology, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany.Germany
期刊
Cancers2023 May 12
原文标识
PubMed 37345075 · DOI 10.3390/cancers15102735