早期肺癌患者外周血CD8+ T细胞和自然杀伤细胞的细胞毒活性较高。
Higher cytotoxic activities of CD8+ T cells and natural killer cells from peripheral blood of early diagnosed lung cancer patients.
发表日期:2023 Aug 14
作者:
Mohamed Labib Salem, Ismail Atia, Nehal M Elmashad
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
细胞毒性(CD8+)和自然杀伤(NK)细胞在抗肿瘤免疫中发挥关键作用。这些细胞的功能失调被认为是肿瘤复发的外源性机制之一。本研究旨在评估肺癌患者化疗前后外周血中CD8+T和NK细胞的细胞毒活性。招募了健康志愿者(n = 5)和肺癌患者(n = 15:化疗前5例,化疗期间5例,化疗后5例)。使用流式细胞术分析新鲜外周血单个核细胞(PBMCs)及其培养72小时后并受到5μg/ml卡那霉素A(Con A)和50ng/ml IL-2刺激后的CD8+T细胞、NK和CD56+T细胞中内源性粒细胞酶B(GzB)的表达水平。此外,使用荧光免疫测定法测量病人血浆中炎症细胞因子的水平。培养后,与对照者以及化疗期间和化疗后的患者相比,肺癌患者化疗前的PBMCs中CD3+、CD4+、CD8+和NKCD8+T细胞表达GzB的细胞数量显著增加。与对照个体相比,化疗前的患者血清中IL-1和CXCL8的水平分别增加了37倍和40倍。化疗期间和化疗后患者的GzB表达和细胞因子水平相似。多克隆刺激PBMCs可以恢复化疗后肺癌患者的细胞毒性CD8和NK细胞的细胞溶解活性。© 2023. BioMed Central Ltd., part of Springer Nature.
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.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.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 CD56+T 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.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.Polyclonal stimulation of PBMCs can restore the cytolytic activities of cytotoxic CD8 and NK cells from lung cancer patients even after chemotherapy.© 2023. BioMed Central Ltd., part of Springer Nature.