Qingjin Desheng Pian attenuates NSCLC progression by suppressing neutrophil extracellular trap formation: involvement of the HMGB1/TLR2/MyD88 axis
Abstract
BackgroundNon-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide. Despite advances in immune checkpoint inhibitor-based therapy, a substantial proportion of patients derive limited benefit. In the tumor microenvironment, neutrophil extracellular traps (NETs) promote tumor progression and metastasis, representing a potential therapeutic target. Qingjin Desheng Pian (QJDS) is a standardized hospital preparation of traditional Chinese medicine that has been used clinically for primary and metastatic lung cancer. Although earlier studies have suggested antitumor effects of QJDS, its impact on NET formation and the underlying mechanisms in NSCLC remain unclear. This study aimed to investigate whether QJDS suppresses NET formation and to elucidate the molecular mechanisms.MethodsThis retrospective study included 209 stage III-IV NSCLC patients who received QJDS plus chemotherapy or chemotherapy alone. NET enrichment was assessed by single-cell RNA sequencing and histopathology. Network pharmacology predicted potential targets. A syngeneic Lewis lung carcinoma model evaluated antitumor efficacy and intratumoral NET levels. In vitro, primary mouse neutrophils were stimulated with phorbol 12-myristate 13-acetate (PMA) for NET induction, followed by QJDS intervention. Transcriptomic sequencing and weighted gene co-expression network analysis identified hub genes. Pharmacological rescue experiments using N4-acetylcytidine (N4A) were performed.ResultsQJDS prolonged progression-free survival, improved quality of life, and attenuated systemic inflammation. NETs were markedly enriched in NSCLC tumor tissues compared with adjacent tissues. QJDS dose-dependently inhibited tumor growth and reduced intratumoral NET formation and serum MPO-DNA levels in vivo. In vitro, QJDS suppressed NET release and attenuated NET-mediated migration, invasion, epithelial-mesenchymal transition (EMT), and proliferation of lung cancer cells. Mechanistically, high mobility group box 1 (HMGB1) was identified as a key hub gene through transcriptomic and weighted gene co-expression network analyses. QJDS significantly downregulated HMGB1, toll-like receptor 2 (TLR2), and myeloid differentiation primary response 88 (MyD88) expression in neutrophils, effects partially reversed by N4A.ConclusionThese findings indicate that QJDS attenuates NSCLC progression by suppressing NET formation through mechanisms involving the HMGB1/TLR2/MyD88 axis, supporting its adjuvant application in advanced lung cancer.
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BibTeX
@article{qin2026qingjin,
title = {{Qingjin Desheng Pian attenuates NSCLC progression by suppressing neutrophil extracellular trap formation: involvement of the HMGB1/TLR2/MyD88 axis}},
author = {Bingbing Qin and Shangyi Huang and Chenlu Ma and Ruisheng Zhou and Daihan Zhou and Ying Tang},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.2000534},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.2000534},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Qingjin Desheng Pian attenuates NSCLC progression by suppressing neutrophil extracellular trap formation: involvement of the HMGB1/TLR2/MyD88 axis
AU - Bingbing Qin
AU - Shangyi Huang
AU - Chenlu Ma
AU - Ruisheng Zhou
AU - Daihan Zhou
AU - Ying Tang
PY - 2026
DA - 2026/11/03
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.2000534
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.2000534
AB - BackgroundNon-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide. Despite advances in immune checkpoint inhibitor-based therapy, a substantial proportion of patients derive limited benefit. In the tumor microenvironment, neutrophil extracellular traps (NETs) promote tumor progression and metastasis, representing a potential therapeutic target. Qingjin Desheng Pian (QJDS) is a standardized hospital preparation of traditional Chinese medicine that has been used clinically for primary and metastatic lung cancer. Although earlier studies have suggested antitumor effects of QJDS, its impact on NET formation and the underlying mechanisms in NSCLC remain unclear. This study aimed to investigate whether QJDS suppresses NET formation and to elucidate the molecular mechanisms.MethodsThis retrospective study included 209 stage III-IV NSCLC patients who received QJDS plus chemotherapy or chemotherapy alone. NET enrichment was assessed by single-cell RNA sequencing and histopathology. Network pharmacology predicted potential targets. A syngeneic Lewis lung carcinoma model evaluated antitumor efficacy and intratumoral NET levels. In vitro, primary mouse neutrophils were stimulated with phorbol 12-myristate 13-acetate (PMA) for NET induction, followed by QJDS intervention. Transcriptomic sequencing and weighted gene co-expression network analysis identified hub genes. Pharmacological rescue experiments using N4-acetylcytidine (N4A) were performed.ResultsQJDS prolonged progression-free survival, improved quality of life, and attenuated systemic inflammation. NETs were markedly enriched in NSCLC tumor tissues compared with adjacent tissues. QJDS dose-dependently inhibited tumor growth and reduced intratumoral NET formation and serum MPO-DNA levels in vivo. In vitro, QJDS suppressed NET release and attenuated NET-mediated migration, invasion, epithelial-mesenchymal transition (EMT), and proliferation of lung cancer cells. Mechanistically, high mobility group box 1 (HMGB1) was identified as a key hub gene through transcriptomic and weighted gene co-expression network analyses. QJDS significantly downregulated HMGB1, toll-like receptor 2 (TLR2), and myeloid differentiation primary response 88 (MyD88) expression in neutrophils, effects partially reversed by N4A.ConclusionThese findings indicate that QJDS attenuates NSCLC progression by suppressing NET formation through mechanisms involving the HMGB1/TLR2/MyD88 axis, supporting its adjuvant application in advanced lung cancer.
SN - 1664-3224
ER -