Evidence map›Paper›PMID 40407494›Full record

ArticleProteomes2025

Small Extracellular Vesicle (sEV) Uptake from Lung Adenocarcinoma and Squamous Cell Carcinoma Alters T-Cell Cytokine Expression and Modulates Protein Profiles in sEV Biogenesis.

Hafiza Padinharayil, Jinsu Varghese, Pulikkottil Raphael Varghese, Cornelia M Wilson, Alex George

Abstract read
In one paragraph

Article in Proteomes, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Hafiza PadinharayilJubilee Mission Medical College & Research Institute, Thrissur 680005, Kerala, India.ORCID 0000-0001-8516-1943
Jinsu VargheseDepartment of Zoology, St. Thomas College, Kozhencherry, Pathanamthitta 689641, Kerala, India.
Pulikkottil Raphael VargheseJubilee Mission Medical College & Research Institute, Thrissur 680005, Kerala, India.
Cornelia M WilsonSchool of Psychology and Life Sciences, Canterbury Christ Church University, Kent CT1 1QU, UK.ORCID 0000-0001-6584-6179
Alex GeorgeJubilee Mission Medical College & Research Institute, Thrissur 680005, Kerala, India.ORCID 0000-0002-4962-3917

Funding

Canterbury Christ Church University P23-0227
6 · The paper itself

Abstract

backgroundDespite advances in immunotherapy, non-small-cell lung carcinoma (NSCLC)'s clinical success is limited, possibly due to substantial immunological alterations in advanced cancer patients. This study examines the immunomodulatory effects of sEVs derived from lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) on T cells.

methodsSEVs were isolated from lung cancer cell lines and Jurkat-E6.1. SEV size and morphology were analyzed by NTA and TEM, respectively, while Western blotting confirmed sEV markers. SEV uptake was assessed, followed by resazurin assay, RNA isolation, quantification, cDNA preparation, RT-PCR, nano LC-MS, and bioinformatic analysis, before and after treating Jurkat-E6.1 cells with sEVs from A549 and SKMES1.

resultsCancer-derived sEVs were efficiently internalized by immune cells, reducing T-cell viability. The real-time PCR analysis showed downregulation of KI67, BCL2, BAX, TNFA, IL6, TGFβ, and IL10, suggesting reduced proliferation, dysregulated apoptosis, and impaired inflammatory and immunosuppressive signaling, and the upregulation of GZMB and IL2 suggests retained cytotoxic potential but possibly dysfunctional T-cell activation. Proteomic analysis revealed 39 differentially abundant proteins (DAPs) in ADC-treated T cells and 276 in SCC-treated T cells, with 19 shared DAPs. Gene Ontology (GO) analysis of these DAPs highlighted processes such as sEV biogenesis, metabolic pathways, and regulatory functions, with ADC sEVs influencing NAD metabolism, ECM binding, and oxidoreductase activity, while SCC sEVs affected mRNA stability, amino acid metabolism, and cadherin binding. The cytoplasmic colocalization suggests the presence of these proteins in the cellular and extracellular lumen, indicating the potential of further release of these proteins in the vesicles by T cells.

conclusionLung cancer-derived sEVs regulate T-cell activities through immunoregulatory signaling. The molecular interactions between sEVs and immune cells can reveal novel tumor immune regulatory mechanisms and therapeutic targets.

Indexed as

cross-treatmentimmune modulationlung adenocarcinomaproteinRNAsEVssquamous cell carcinomaT cells

Identifiers

PMID40407494
PMCPMC12101295

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.