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已发表论文
肿瘤浸润性肥大细胞通过调控硬化性微环境增强 ESCC 新辅助治疗疗效
Authors Cui X, Zhang X, Zhao Q, Chen X, He M, Zhang M, Yang R, Zhao J, Liu J
Received 29 August 2025
Accepted for publication 9 December 2025
Published 14 January 2026 Volume 2026:19 564090
DOI https://doi.org/10.2147/OTT.S564090
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Tohru Yamada
Xing Cui,1,* Xiangmei Zhang,2,3,* Qi Zhao,1 Xin Chen,1,3 Ming He,1,3 Meng Zhang,4 Ruiling Yang,5 Jidong Zhao,1,3 Junfeng Liu1
1Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, People’s Republic of China; 2Cancer Institute of Hebei Province, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, People’s Republic of China; 3Hebei Provincial Key Laboratory of Tumor Microenvironment and Drug Resistance, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China; 4Department of Clinical Lab, Affiliated Hospital of Hebei University, Baoding, 071000, People’s Republic of China; 5Department of Breast Surgery, Handan Central Hospital, Handan, Hebei, 056000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Jidong Zhao, Email ud1291@126.com Junfeng Liu, Email 18939111700@189.cn
Objective: Neoadjuvant therapy is essential for locally advanced esophageal squamous cell carcinoma (ESCC), but its efficacy requires improvement. This study investigated the role of tumor-infiltrating mast cells (MCs) in treatment response and prognosis.
Methods: An integrated approach was employed, combining single-cell RNA sequencing of paired specimens from one ESCC patient pre- and post-neoadjuvant therapy, immunofluorescence analysis of a retrospective cohort of 68 treatment-naïve ESCC surgical specimens, bioinformatics analysis of public datasets, and in vitro mast cell activation assays.
Results: Single-cell sequencing revealed a post-therapy increase in the proportion of MCs among immune cells (4% to 12%), alongside an enriched inflammatory gene profile. In the cohort of 68 patients, higher MC density was associated with smaller tumor diameter (Pearson r = − 0.32, p=0.007) and significantly better overall survival (36 vs 23.5 months, p=0.038). No such correlations were found for macrophages or CD8+ T cells. Bioinformatic analysis linked MCs to extracellular matrix and vascular smooth muscle regulation. Critically, high MC density combined with low desmoplasia or fibrosis identified patients with the most favorable prognosis. Phenotypically, MCs were predominantly non-degranulated in situ. In vitro, LPS activation (a non-degranulating signal) significantly upregulated CCL19 and other chemokines in mast cells. Furthermore, LPS was detected in the tumor stroma of 47.1% (32/68) of patients but not in normal mucosa.
Conclusion: The findings demonstrate that tumor-infiltrating MCs are associated with enhanced efficacy of neoadjuvant therapy and improved survival in ESCC. The mechanism may involve LPS-induced, non-degranulatory MC activation that modulates the desmoplastic microenvironment. Targeting this axis presents a promising strategy for ESCC treatment.
Keywords: tumor-infiltrating mast cells, desmoplasia, neoadjuvant therapy, non-degranulation, efficacy
1Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, People’s Republic of China; 2Cancer Institute of Hebei Province, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, People’s Republic of China; 3Hebei Provincial Key Laboratory of Tumor Microenvironment and Drug Resistance, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China; 4Department of Clinical Lab, Affiliated Hospital of Hebei University, Baoding, 071000, People’s Republic of China; 5Department of Breast Surgery, Handan Central Hospital, Handan, Hebei, 056000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Jidong Zhao, Email ud1291@126.com Junfeng Liu, Email 18939111700@189.cn
Objective: Neoadjuvant therapy is essential for locally advanced esophageal squamous cell carcinoma (ESCC), but its efficacy requires improvement. This study investigated the role of tumor-infiltrating mast cells (MCs) in treatment response and prognosis.
Methods: An integrated approach was employed, combining single-cell RNA sequencing of paired specimens from one ESCC patient pre- and post-neoadjuvant therapy, immunofluorescence analysis of a retrospective cohort of 68 treatment-naïve ESCC surgical specimens, bioinformatics analysis of public datasets, and in vitro mast cell activation assays.
Results: Single-cell sequencing revealed a post-therapy increase in the proportion of MCs among immune cells (4% to 12%), alongside an enriched inflammatory gene profile. In the cohort of 68 patients, higher MC density was associated with smaller tumor diameter (Pearson r = − 0.32, p=0.007) and significantly better overall survival (36 vs 23.5 months, p=0.038). No such correlations were found for macrophages or CD8+ T cells. Bioinformatic analysis linked MCs to extracellular matrix and vascular smooth muscle regulation. Critically, high MC density combined with low desmoplasia or fibrosis identified patients with the most favorable prognosis. Phenotypically, MCs were predominantly non-degranulated in situ. In vitro, LPS activation (a non-degranulating signal) significantly upregulated CCL19 and other chemokines in mast cells. Furthermore, LPS was detected in the tumor stroma of 47.1% (32/68) of patients but not in normal mucosa.
Conclusion: The findings demonstrate that tumor-infiltrating MCs are associated with enhanced efficacy of neoadjuvant therapy and improved survival in ESCC. The mechanism may involve LPS-induced, non-degranulatory MC activation that modulates the desmoplastic microenvironment. Targeting this axis presents a promising strategy for ESCC treatment.
Keywords: tumor-infiltrating mast cells, desmoplasia, neoadjuvant therapy, non-degranulation, efficacy