人恶性胸腔积液中FOXP3+CD3+CD56+自然杀伤T (NKT)样细胞表型和代谢特征的改变

IF 7.2 2区医学

Oncoimmunology Pub Date : 2023-01-01 DOI:10.1080/2162402X.2022.2160558

Zi-Hao Wang, Pei Zhang, Wen-Bei Peng, Lin-Lin Ye, Xuan Xiang, Xiao-Shan Wei, Yi-Ran Niu, Si-Yu Zhang, Qian-Qian Xue, Hao-Lei Wang, Qiong Zhou

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引用次数: 2

摘要

恶性胸腔积液(MPE)是一种功能性的“冷”肿瘤微环境，其中CD8+ T细胞和自然杀伤T (NKT)样细胞的抗肿瘤活性被抑制，而调节性T (Treg)细胞的功能被增强。通过流式细胞术和免疫荧光染色，我们检测到MPE中表达FOXP3的nkt样细胞的独特亚群。通过单细胞RNA测序(scRNA-seq)分析，我们发现FOXP3+ nkt样细胞的糖酵解途径和丙酮酸代谢高度激活。与Treg细胞类似，FOXP3+ nkt样细胞高度表达单羧酸转运蛋白1 (MCT1)和乳酸脱氢酶B，以摄取和利用乳酸，从而维持其在MPE中的免疫抑制功能和高乳酸化。此外，我们发现MCT1小分子抑制剂7ACC2在体外可显著降低nkt样细胞中FOXP3的表达和组蛋白乳酸化水平。总之，我们首次揭示了人MPE中FOXP3+ nkt样细胞表型和代谢特征的改变。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Altered phenotypic and metabolic characteristics of FOXP3+CD3+CD56+ natural killer T (NKT)-like cells in human malignant pleural effusion.

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Altered phenotypic and metabolic characteristics of FOXP3⁺CD3⁺CD56⁺ natural killer T (NKT)-like cells in human malignant pleural effusion.

Malignant pleural effusion (MPE) is a functional 'cold' tumor microenvironment in which the antitumor activity of CD8⁺ T cells and natural killer T (NKT)-like cells is suppressed and the function of regulatory T (T_reg) cells is enhanced. Using flow cytometry and immunofluorescence staining, we detected a distinct subset of NKT-like cells expressing FOXP3 in MPE. Through single-cell RNA sequencing (scRNA-seq) analysis, we found that the glycolysis pathway and pyruvate metabolism were highly activated in FOXP3⁺ NKT-like cells. Similar to T_reg cells, FOXP3⁺ NKT-like cells highly expressed monocarboxylate transporter 1 (MCT1) and lactate dehydrogenase B to uptake and utilize lactate, thereby maintaining their immunosuppressive function and hyperlactylation in MPE. Furthermore, we found that MCT1 small molecule inhibitor 7ACC2 significantly reduced FOXP3 expression and histone lactylation levels in NKT-like cells in vitro. In conclusion, we reveal for the first time the altered phenotypic and metabolic features of FOXP3⁺ NKT-like cells in human MPE.

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来源期刊

Oncoimmunology ONCOLOGY-IMMUNOLOGY

CiteScore

12.80

自引率

2.80%

发文量

276

期刊介绍： Tumor immunology explores the natural and therapy-induced recognition of cancers, along with the complex interplay between oncogenesis, inflammation, and immunosurveillance. In response to recent advancements, a new journal, OncoImmunology, is being launched to specifically address tumor immunology. The field has seen significant progress with the clinical demonstration and FDA approval of anticancer immunotherapies. There's also growing evidence suggesting that many current chemotherapeutic agents rely on immune effectors for their efficacy. While oncologists have historically utilized chemotherapeutic and radiotherapeutic regimens successfully, they may have unwittingly leveraged the immune system's ability to recognize tumor-specific antigens and control cancer growth. Consequently, immunological biomarkers are increasingly crucial for cancer prognosis and predicting chemotherapy efficacy. There's strong support for combining conventional anticancer therapies with immunotherapies. OncoImmunology will welcome high-profile submissions spanning fundamental, translational, and clinical aspects of tumor immunology, including solid and hematological cancers, inflammation, and both innate and acquired immune responses.