TOB1 modulates neutrophil phenotypes to influence gastric cancer progression and immunotherapy efficacy

Sep 21, 2026

TOB1 is investigated as an ERBB2.1 transducer protein with tumor-suppressive properties in gastric cancer, while also negatively regulating immune-cell activation and growth. The study quantifies TOB1 expression in immune populations in gastric cancer tissue microarrays using multiplex immunofluorescence, and links nuclear/cytoplasmic TOB1 in CD66b+ neutrophils to clinical prognosis by Cox analyses. Functional co-culture experiments with si-TOB1 neutrophils evaluate neutrophil apoptosis and the resulting malignant phenotype in gastric cancer cell models, supported by TCGA/TIMER2 dataset analyses. Higher TOB1-associated neutrophils correlate with improved immunotherapy response.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Introduction

Methods

Results

Discussion

Keywords

TYPE Original Research PUBLISHED 28 March 2024 DOI 10.3389/fimmu.2024.1369087 OPEN ACCESS EDITED BY Wantao Wu, Central South University, China REVIEWED BY Yun Liu, Guangzhou Medical University, China Fengrui Yang, University of Science and Technology of China, China Min Mao, Army Medical University, China *CORRESPONDENCE Jingcui Yu [yujingcui@ems.hrbmu.edu.cn](yujingcui@ems.hrbmu.edu.cn) RECEIVED 11 January 2024 ACCEPTED 15 March 2024 PUBLISHED 28 March 2024 CITATION Zhang J, Li Y, Chen J, Huang T, Lin J, Pi Y, Hao H, Wang D, Liang X, Fu S and Yu J (2024) TOB1 modulates neutrophil phenotypes to inﬂuence gastric cancer progression and immunotherapy efﬁcacy. Front. Immunol. 15:1369087 . doi: 10.3389/fimmu.2024.1369087 COPYRIGHT © 2024 Zhang, Li, Chen, Huang, Lin, Pi, Hao, Wang, Liang, Fu and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TOB1 modulates neutrophil phenotypes to inﬂuence gastric cancer progression and immunotherapy efﬁcacy Jinfeng Zhang 1, Yunlong Li 2, Jing Chen 3, Tongtong Huang 1, Jing Lin 1, Yilin Pi 3, Huiting Hao 4, Dong Wang 1, Xiao Liang 5, Songbin Fu 5 and Jingcui Yu 1,5* 1Scientiﬁc Research Center, The Second Afﬁliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China, 2 Department of General Surgery, The Second Afﬁliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China, 3 Department of Gastroenterology, The Second Afﬁliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China, 4 Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China, 5 Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China, Harbin Medical University, Ministry of Education, Harbin, China Introduction: The ErbB-2 . 1(TOB1) signaling transducer protein is a tumorsuppressive protein that actively suppresses the malignant phenotype of gastric cancer cells. Yet, TOB1 negatively regulates the activation and growth of different immune cells. Understanding the expression and role of TOB1 in the gastric cancer immune environment is crucial to maximize its potential in targeted immunotherapy. Methods: This study employed multiplex immunoﬂuorescence analysis to precisely delineate and quantify the expression of TOB1 in immune cells within gastric cancer tissue microarrays. Univariate and multivariate Cox analyses were performed to assess the inﬂuence of clinical-pathological parameters, immune cells, TOB1, and double-positive cells on the prognosis of gastric cancer patients. Subsequent experiments included co-culture assays of si-TOB1-transfected neutrophils with AGS or HGC-27 cells, along with EdU, invasion, migration assays, and bioinformatics analyses, aimed at elucidating the mechanisms through which TOB1 in neutrophils impacts the prognosis of gastric cancer patients. Results: We remarkably revealed that TOB1 exhibits varying expression levels in both the nucleus (nTOB1) and cytoplasm (cTOB1) of diverse immune cell populations, including CD8 + T cells, CD66b+ neutrophils, FOXP3 + Tregs, CD20+ B cells, CD4+ T cells, and CD68+ macrophages within gastric cancer and paracancerous tissues. Signiﬁcantly, TOB1 was notably concentrated in CD66b+ neutrophils. Survival analysis showed that a higher density of cTOB1/ nTOB1+CD66b+ neutrophils was linked to a better prognosis. Subsequent experiments revealed that, following stimulation with the supernatant of tumor tissue culture, the levels of TOB1 protein and mRNA in neutrophils decreased, accompanied by enhanced apo

FAQs

What role does TOB1 play in gastric cancer according to the study?

TOB1 is described as a tumorsuppressive protein that suppresses malignant gastric cancer phenotypes and modulates immune-cell activity within the tumor microenvironment.

How was TOB1 expression measured in the immune context of gastric cancer?

TOB1 expression in immune cells within gastric cancer tissue microarrays was delineated and quantified using multiplex immunofluorescence analysis, including nuclear and cytoplasmic localization.

What did the study find about TOB1 in neutrophils and patient prognosis or therapy response?

TOB1 was notably concentrated in CD66b+ neutrophils, and higher levels of cTOB1/nTOB1+CD66b+ neutrophils were linked to better prognosis and improved immunotherapy response in TCGA/TIMER2 analyses.

Sep 21, 2026

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