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Background <p>STAT4 is a key transcription factor in T helper (TH) cell differentiation and immune response regulation, playing a vital role in antitumor immunity. However, its role in modulating immune cell interactions, oxidative stress, and epigenetic control in non-small cell lung cancer (NSCLC) remains incompletely understood.</p> Methods and results <p>Peripheral blood mononuclear cells (PBMCs) from healthy donors and NSCLC patients underwent CRISPR/Cas9-mediated STAT4 knockout and plasmid-based overexpression. Flow cytometry assessed T–B cell interaction markers, while biochemical assays measured oxidative stress markers including nitric oxide and glutathione. Cytokine profiles were evaluated using ELISA, and epigenetic modifications were analyzed through chromatin immunoprecipitation (ChIP-qPCR) and RNA–DNA hybrid immunoprecipitation techniques. DNA and RNA methylation were quantified, and cytotoxicity was assessed via LDH release. STAT4 overexpression increased T–B cell marker expression (CD4, CD5, CD19, CD23) and elevated TH cytokine levels. STAT4 depletion induced oxidative stress, increased R-loop formation, reduced m6A RNA methylation, and altered DNA methylation patterns. Epigenetic analysis revealed decreased H3K27me3 and increased H3K4me3 at TH1 loci following STAT4 overexpression. LDH assays demonstrated enhanced cancer cytotoxicity in STAT4-overexpressing PBMCs.</p> Conclusions <p>STAT4 integrates immune signaling, epigenetic remodeling, and oxidative balance to enhance antitumor immunity in NSCLC. Therapeutic modulation of STAT4 represents a promising strategy to improve immune responses in NSCLC treatment.</p>

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STAT4 mediated modulation of T–B cell interactions profiling: enhances antitumor immunity in non-small cell lung cancer (NSCLC)

  • 期刊论文

  • 发表日期：

    2026年2月14日

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  • Roshni Bibi,
  • Melvin George,
  • Koustav Sarkar

摘要

Background

STAT4 is a key transcription factor in T helper (TH) cell differentiation and immune response regulation, playing a vital role in antitumor immunity. However, its role in modulating immune cell interactions, oxidative stress, and epigenetic control in non-small cell lung cancer (NSCLC) remains incompletely understood.

Methods and results

Peripheral blood mononuclear cells (PBMCs) from healthy donors and NSCLC patients underwent CRISPR/Cas9-mediated STAT4 knockout and plasmid-based overexpression. Flow cytometry assessed T–B cell interaction markers, while biochemical assays measured oxidative stress markers including nitric oxide and glutathione. Cytokine profiles were evaluated using ELISA, and epigenetic modifications were analyzed through chromatin immunoprecipitation (ChIP-qPCR) and RNA–DNA hybrid immunoprecipitation techniques. DNA and RNA methylation were quantified, and cytotoxicity was assessed via LDH release. STAT4 overexpression increased T–B cell marker expression (CD4, CD5, CD19, CD23) and elevated TH cytokine levels. STAT4 depletion induced oxidative stress, increased R-loop formation, reduced m6A RNA methylation, and altered DNA methylation patterns. Epigenetic analysis revealed decreased H3K27me3 and increased H3K4me3 at TH1 loci following STAT4 overexpression. LDH assays demonstrated enhanced cancer cytotoxicity in STAT4-overexpressing PBMCs.

Conclusions

STAT4 integrates immune signaling, epigenetic remodeling, and oxidative balance to enhance antitumor immunity in NSCLC. Therapeutic modulation of STAT4 represents a promising strategy to improve immune responses in NSCLC treatment.