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

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

doi:10.1186/s12935-024-03569-x

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

Cancer Cell Int. 2024 Nov 23;24(1):389. doi: 10.1186/s12935-024-03569-x.

Authors

Chae Bok Lee^#¹, Hei Gwon Choi^{2

3}, Sintayehu Kebede Gurmessa⁴, In-Taek Jang¹, Naresh Kumar⁵, Zongyou Jiang¹, Nagendra Kumar Kaushik⁶, Hwa-Jung Kim⁷

Affiliations

¹ Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, 35015, Korea.
² Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon, 35015, Korea.
³ Department of Medical Sciences, Chungnam National University, Daejeon, 35015, Korea.
⁴ Department of Molecular Microbiology and Immunology, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.
⁵ Department of Medical Devices, National Institute of Pharmaceutical Education and Research Guwahati (NIPER-G), Kamrup, Assam, 781101, India.
⁶ Department of Electrical and Biological Physics, Plasma Bioscience Research Center, Kwangwoon University, Seoul, 01897, Korea.
⁷ Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, 35015, Korea. hjukim@cnu.ac.kr.

^# Contributed equally.

PMID: 39580412
DOI: 10.1186/s12935-024-03569-x

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.

Keywords: Cancer immunogenic cell death; Dendritic cell activation; Lewis Lung cancer cells; Non-thermal plasma-treated medium; Programmed death-ligand 1; Reactive oxygen species.

Abstract

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