基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
T 细胞免疫球蛋白黏蛋白-3 及其配体半乳糖凝集素-9 表达水平对三阴性乳腺癌无复发生存的预后意义
英文原题：Prognostic significance of the expression levels of T-cell immunoglobulin mucin-3 and its ligand galectin-9 for relapse-free survival in triple-negative breast cancer.
查看英文原题
Prognostic significance of the expression levels of T-cell immunoglobulin mucin-3 and its ligand galectin-9 for relapse-free survival in triple-negative breast cancer.
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中文摘要
T细胞表面表达的T细胞免疫球蛋白黏蛋白-3（TIM-3）与其配体galectin-9结合时作为免疫检查点发挥作用。阻断TIM-3/galectin-9信号通路的免疫抑制可能为癌症免疫治疗提供新的治疗途径。与此一致，TIM-3表达与多种不同类型癌症的较差预后相关，可能是由于对抗癌免疫监视的抑制。目前多项研究已记录免疫检查点阻断即使在高侵袭性的三阴性乳腺癌（TNBC）中也具有一定疗效。
然而，临床反应相对较弱，提示可能涉及多种不同通路。在此背景下，TIM-3/galectin-9检查点在TNBC中的作用尚不明确。
本研究旨在确定TIM-3和galectin-9表达在该癌症中的临床病理意义。为此，对62例在日本关西医科大学医院（枚方市）接受手术但未接受新辅助化疗的TNBC患者进行了检查。采用组织微阵列进行免疫组化，分析TIM-3和galectin-9表达的相关性及其相对于其他不良预后风险因素对无复发生存的影响。在62例患者样本中，49例（79%）检测到galectin-9表达，30例（48.4%）检测到TIM-3表达。肿瘤细胞galectin-9表达与更有利的预后相关（P=0.027），TIL（肿瘤浸润淋巴细胞）上TIM-3表达亦如此（P=0.007）。多变量分析表明，与galectin-9和/或TIM-3阴性相比，galectin-9和TIM-3双阳性与更有利的预后显著相关（P=0.044）。
因此，TIM-3/galectin-9信号通路可能影响TNBC患者肿瘤微环境中的抗肿瘤免疫反应。需要进一步研究以确定这些关系背后的分子机制。
展开英文摘要原文
T-cell immunoglobulin mucin-3 (TIM-3) expressed at the T-cell surface acts as an immune checkpoint when bound by its ligand galectin-9. Blockade of immunosuppression by the TIM3/galectin-9 signalling pathway may offer novel therapeutic approaches for cancer immunotherapy.
Consistent with this, TIM-3 expression is associated with poorer prognosis in several different types of cancer, possibly as a result of suppression of anticancer immunosurveillance. A number of studies have now documented some effectiveness of immune checkpoint blockade even in triple-negative breast cancer (TNBC), which is highly aggressive.
However, clinical responses are relatively weak, suggesting that several different pathways may be involved. In this context, the role of the TIM-3/galectin-9 checkpoint in TNBC is not clear. The present study aimed to determine the clinicopathological significance of TIM-3 and galectin-9 expression in this cancer. To this end, 62 patients with TNBC undergoing surgery at Kansai Medical University Hospital (Hirakata, Japan), but not given neoadjuvant chemotherapy, were examined.
Tissue microarrays were employed for immunohistochemistry to analyse associations of TIM-3 and galectin-9 expression and their impact on relapse-free survival relative to other poor prognostic risk factors. Galectin-9 expression was detected in 49 of 62 patient samples (79%), and TIM-3 in 30 of them (48. 4%).
Tumour cell galectin-9 expression was associated with a more favourable prognosis (P=0. 027) as was TIM-3 expression on tumour-infiltrating lymphocytes (P=0. 007). Multivariate analysis indicated that galectin-9- and TIM-3-double-positivity was significantly associated with a more favourable prognosis compared with galectin-9 and/or TIM-3 negativity (P=0. 044).
Thus, the TIM-3/galectin-9 signalling pathway may impact anticancer immune reactions in the tumour microenvironment of patients with TNBC.
Further investigation will be necessary to determine the molecular mechanisms underlying these relationships.
论文信息
- 作者
- Yoshikawa K、Ishida M、Yanai H、Tsuta K、Sekimoto M、Sugie T
- 第一作者单位
- Department of Pathology and Division of Diagnostic Pathology, Kansai Medical University, Hirakata, Osaka 573-1191, Japan.Japan
- 通讯作者单位
- Department of Surgery, Kansai Medical University, Hirakata, Osaka 573-1191, Japan.Japan
- 期刊
- Oncology letters2022 Jun
- 原文标识
- PubMed 35572493 · DOI 10.3892/ol.2022.13318
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