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早期诊断肺癌患者外周血中 CD8 T 细胞和自然杀伤细胞的更高细胞毒性活性。

Higher cytotoxic activities of CD8 T cells and natural killer cells from peripheral blood of early diagnosed lung cancer patients.

机构信息

Zoology Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt.

Center of Excellence in Cancer Research, New Tanta University Teaching Hospital, Tanta, Egypt.

出版信息

BMC Immunol. 2023 Aug 14;24(1):24. doi: 10.1186/s12865-023-00553-4.

Abstract

INTRODUCTION

Cytotoxic (CD8+) and natural killer (NK) cells play critical roles in anti-tumor immunity. Dysfunction in these cells is considered as one of the extrinsic mechanisms for tumor relapse.

AIM

We aimed in this study to assess cytotoxic activities of CD8 + T and NK cells in the peripheral blood from lung cancer patients before and after induction of chemotherapy.

SUBJECTS AND METHODS

Healthy (n = 5) volunteers and lung cancer patients (n = 15:5 before, 5 during, and 5 after induction of chemotherapy) were recruited. Flow cytometry was used to analyze the numbers of CD8 + T cells, NK and CD56T cells and their intracellular expression of granzyme B (GzB) in fresh peripheral blood mononuclear cells (PBMCs) and after 72 h of their culture in vitro and stimulation with 5 µg/ml Concanavalin A (Con A) and 50ng/ml IL-2). In addition, the plasma levels of inflammatory cytokines were measured using luminex.

RESULTS

After culture, significant increases in the number of GzB expressing cells gated on CD3+, CD4+, CD8 + and NKCD8 + T cells in the PBMCs from lung cancer patients before induction of chemotherapy as compared to control individuals as well as patients during and after induction of chemotherapy. Serum levels of IL-1 and CXCL8 in patients before induction of chemotherapy showed 37- and 40-fold increases, respectively, as compared to control individuals. Both GzB expression and cytokines levels in patients during and after chemotherapy were similar.

CONCLUSION

Polyclonal stimulation of PBMCs can restore the cytolytic activities of cytotoxic CD8 and NK cells from lung cancer patients even after chemotherapy.

摘要

简介

细胞毒性(CD8+)和自然杀伤(NK)细胞在抗肿瘤免疫中发挥着关键作用。这些细胞的功能障碍被认为是肿瘤复发的外在机制之一。

目的

本研究旨在评估化疗诱导前后肺癌患者外周血中 CD8+T 和 NK 细胞的细胞毒性活性。

受试者和方法

招募了 5 名健康志愿者和 15 名肺癌患者(5 名在化疗诱导前、5 名在化疗诱导期间、5 名在化疗诱导后)。使用流式细胞术分析新鲜外周血单核细胞(PBMC)中 CD8+T 细胞、NK 和 CD56T 细胞的数量及其细胞内颗粒酶 B(GzB)的表达,以及在体外培养 72 小时后用 5μg/ml 刀豆蛋白 A(Con A)和 50ng/ml IL-2 刺激后的表达情况。此外,使用 Luminex 测量血浆中炎症细胞因子的水平。

结果

与对照组和化疗诱导期间和之后的患者相比,化疗诱导前的肺癌患者 PBMC 中 CD3+、CD4+、CD8+和 NKCD8+T 细胞中表达 GzB 的细胞数量在培养后显著增加。化疗诱导前患者的血清 IL-1 和 CXCL8 水平分别比对照组增加了 37 倍和 40 倍。化疗诱导期间和之后的患者的 GzB 表达和细胞因子水平相似。

结论

即使在化疗后,多克隆刺激 PBMC 也可以恢复肺癌患者的细胞毒性 CD8 和 NK 细胞的细胞毒性活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e903/10426146/8c7e60ef424b/12865_2023_553_Fig1_HTML.jpg

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