PXD059688

PXD059688 is an original dataset announced via ProteomeXchange.

Title	High-dose ascorbic acid synergizes with anti-PD1 therapy in non-small cell lung cancer in vitro and in vivo models
Description	Introduction: Immune checkpoint inhibitors(ICIs) targeting programmed cell death protein 1 (PD1) confer significant survival benefits to patients with non-small cell lung cancer (NSCLC). However, there remains a substantial unmet need to identify therapeutic approaches to overcome resistance and provide benefits to these patients. High-dose ascorbic acid (AA) acts synergistically with many standard anticancer treatments. However, little is known about the effect of high-dose AA on improving the efficacy of anti-PD1 inhibitors in NSCLC. This study aimed to elucidate the effects of high-dose AA on anti-PD1 immunotherapy in NSCLC. Methods: The combined effects of high-dose AA and anti-PD1 were investigated using a coculture model of H460 cells and CD8+ T cells and an LLC1 lung cancer syngeneic mouse model. To investigate the molecular mechanism, tumor tissues from mice were analyzed by comprehensive proteomic profiling using nano-LC-ESI-MS/MS. Results: Pretreatment with a high dose of AA led to enhanced the sensitivity to the cytotoxicity of CD8+ T cells derived from healthy donor for H460 cells. Additionally, the combination of anti-PD1 and high-dose AA significantly increased CD8+ T cell cytotoxicity in H460 cells. The combination of anti-PD1 and high-dose AA showed dramatic antitumor effects in a syngeneic mouse model of lung cancer by significantly reducing tumor growth and increasing CD8+ T cell-dependent cytotoxicity and macrophage activity. Comprehensive protein analysis confirmed that high-dose AA in anti-PD1-treated tumor tissues enhanced the antitumor effects by regulating various immune-related mechanisms, including the B cell and T cell receptor signaling pathways, Fc gamma R-mediated phagocytosis, and natural killer (NK) cell-mediated cytotoxicity. Discussion: Our results suggest that high-dose AA may be a promising adjuvant to potentiate the efficacy of anti-PD1 immunotherapy.
HostingRepository	PRIDE
AnnounceDate	2025-01-15
AnnouncementXML	Submission_2025-01-14_21:36:47.635.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD059688
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Hak Su Kim
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-12 18:10:38	ID requested
⏵ 1	2025-01-14 21:36:48	announced

10.6019/PXD059688;

10.3389/FIMMU.2024.1512605;

submitter keyword: LC-MSMS,Mouse, lung cancer

Taekyu Lim
contact affiliation	Division of Hematology-Oncology, Department of Internal Medicine, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea
contact email	imegene@naver.com
lab head
Hak Su Kim
contact affiliation	Veterans Medical Research Institute, Veterans Health Service Medical Center
contact email	khs401@bohun.or.kr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/01/PXD059688

PRIDE project URI

• PRIDE
  1. PXD059688
     1. Label: PRIDE project
     2. Name: High-dose ascorbic acid synergizes with anti-PD1 therapy in non-small cell lung cancer in vitro and in vivo models