Enhancing antitumor immunity in Lewis lung cancer through plasma-treated medium-induced activation of dendritic cells.

IF 5.3 2区医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2024-11-23 DOI:10.1186/s12935-024-03569-x

Chae Bok Lee, Hei Gwon Choi, Sintayehu Kebede Gurmessa, In-Taek Jang, Naresh Kumar, Zongyou Jiang, Nagendra Kumar Kaushik, Hwa-Jung Kim

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Abstract

Background: Recently, atmospheric non-thermal plasma jet-treated medium (PTM) has been recognized as a novel strategy in cancer therapy and lymphocyte activation. However, PTM has limitations in inducing a robust antitumor-immune response. This study demonstrated that PTM treatment inhibited tumor progression by activating dendritic cells (DCs).

Method: In this study, we investigated the effects of PTM on selective cytotoxicity and intracellular reactive oxygen species (ROS) generation and oxidative stress-mediated signaling (e.g., glutathione peroxidase, catalase) using respective fluorescence probes in Lewis lung cancer (LLC) cells. Then, the PTM affects the expression of interferon-gamma (IFN)-γ-induced programmed death-ligand 1 (PD-L1) and inhibition of signal transducer and activator of transcription 1 (STAT1) in LLC cells using immunoblotting. Additionally, PTM effects on the tumor cell's death and activation of DCs were done by co-culturing DCs with or without tumor cells. Further, a mouse model was used to evaluate the synergistic antitumor effects of PTM and DCs where tumors are grown under the skin.

Results: PTM-exposed tumor cells increase intracellular superoxide production, enhancing ROS generation and leading to cancer immunogenic cell death. In addition, PTM suppresses IFN-γ-induced PD-L1 expression and STAT1 activation in tumor cells. The activation of DCs induced by PTM is downregulated when these cells are co-cultured with tumor cells. In vivo, intraperitoneal injection of PTM-activated DCs, as a synergistic agent to intertumoral PTM treatment, led to increased CD4⁺ and CD8⁺ T cell infiltration into the tumor and spleen and eventually decreased tumor growth.

Conclusion: Overall, this research introduces a promising avenue for improving lung cancer treatment using PTM to stimulate an immune response and induce cell death in tumor cells. Further studies will be essential to validate these findings and explore clinical applications.

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通过血浆处理培养基诱导的树突状细胞激活增强路易斯肺癌的抗肿瘤免疫力

背景：最近，常压非热等离子体喷射处理介质（PTM）被认为是癌症治疗和淋巴细胞活化的一种新策略。然而，PTM 在诱导强有力的抗肿瘤免疫反应方面存在局限性。本研究表明，PTM 处理可通过激活树突状细胞（DCs）抑制肿瘤进展：本研究利用荧光探针研究了 PTM 对路易斯肺癌（LLC）细胞选择性细胞毒性、细胞内活性氧（ROS）生成和氧化应激介导的信号转导（如谷胱甘肽过氧化物酶、过氧化氢酶）的影响。然后，使用免疫印迹法检测 PTM 对γ-干扰素（IFN）-γ 诱导的程序性死亡配体 1（PD-L1）的表达以及对信号转导子和转录激活子 1（STAT1）的抑制作用。此外，还通过与或不与肿瘤细胞共培养直流细胞，研究了PTM对肿瘤细胞死亡和直流细胞活化的影响。此外，还利用小鼠模型评估了 PTM 和 DCs 的协同抗肿瘤效应，即肿瘤在皮下生长：结果：暴露于 PTM 的肿瘤细胞会增加细胞内超氧化物的产生，从而增强 ROS 的生成并导致癌症免疫原性细胞死亡。此外，PTM 还能抑制 IFN-γ 诱导的肿瘤细胞 PD-L1 表达和 STAT1 激活。当直流细胞与肿瘤细胞共培养时，PTM 诱导的直流细胞活化会被下调。在体内，腹腔注射PTM激活的DC作为瘤间PTM治疗的增效剂，可增加CD4+和CD8+T细胞对肿瘤和脾脏的浸润，并最终减少肿瘤生长：总之，这项研究为利用 PTM 刺激免疫反应并诱导肿瘤细胞死亡来改善肺癌治疗开辟了一条前景广阔的途径。进一步的研究对于验证这些发现和探索临床应用至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.