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TIM-3 细胞毒性肿瘤浸润淋巴细胞分布低预示胃肠道间质瘤预后不良。

Low Distribution of TIM-3 Cytotoxic Tumor-Infiltrating Lymphocytes Predicts Poor Outcomes in Gastrointestinal Stromal Tumors.

机构信息

Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

J Immunol Res. 2021 Feb 17;2021:6647292. doi: 10.1155/2021/6647292. eCollection 2021.

Abstract

There are multiple tumor-infiltrating lymphocytes (TILs) and relevant immune checkpoints existing in gastrointestinal stromal tumor (GIST), which provides opportunities and rationales for developing effective immunotherapies. Recent studies have suggested that checkpoint TIM-3/Gal-9 plays a pivotal role on immune response in multiple tumors, similar to the PD-1/PD-L1, emerging as a potential therapeutic target. However, their functions in GIST are unrevealed. Hence, the expression of immune checkpoints TIM-3 and Gal-9, as well as the infiltration of CD8 T cells and NK cells, is described in 299 cases of GIST specimens. The results showed that TIM-3 and Gal-9 are mainly expressed in TILs, rarely in tumor cells. Expression levels of TIM-3 and Gal-9 significantly differ in varying risks of GIST and exert opposite distribution trends. Indicated by prognosis analysis, high TIM-3 expression of TILs was associated with improved outcome, while low expression levels of TIM-3 in combination with low amounts of CD8 and CD56 TILs predict extremely poor survival. The integrated analysis of TIM-3, CD8, and CD56 TILs as one biomarker is a reliable independent predictor of prognosis. In conclusion, low densities of TIM-3 TILs are associated with poor survival, and integrated immune biomarkers lead to superior predictors of GIST prognosis.

摘要

胃肠道间质瘤(GIST)中存在多种肿瘤浸润淋巴细胞(TILs)和相关免疫检查点,为开发有效的免疫疗法提供了机会和理论依据。最近的研究表明,检查点 TIM-3/Gal-9 在多种肿瘤的免疫反应中发挥着关键作用,类似于 PD-1/PD-L1,成为潜在的治疗靶点。然而,它们在 GIST 中的功能尚未被揭示。因此,研究人员在 299 例 GIST 标本中描述了免疫检查点 TIM-3 和 Gal-9 的表达以及 CD8 T 细胞和 NK 细胞的浸润情况。结果表明,TIM-3 和 Gal-9 主要在 TILs 中表达,在肿瘤细胞中很少表达。TIM-3 和 Gal-9 的表达水平在不同风险的 GIST 中存在显著差异,并呈现出相反的分布趋势。预后分析表明,TILs 中 TIM-3 的高表达与较好的预后相关,而 TIM-3 表达水平低且 CD8 和 CD56 TILs 数量少则预示着极差的生存。TIM-3、CD8 和 CD56 TILs 的综合分析作为一个生物标志物是预后的可靠独立预测因子。总之,TIM-3 TILs 的低密度与不良生存相关,而综合免疫生物标志物则能更好地预测 GIST 的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05bb/7907748/56f9fbef319a/JIR2021-6647292.001.jpg

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