Pub Date : 2026-02-01DOI: 10.1016/j.jare.2026.01.082
Wenbo Zheng, Zepang Sun, Wei Wang, James Edward Han, Md Tauhidul Islam, Wencheng Li, Qingyu Yuan, Chuanli Chen, Sujuan Xi, Zihan Li, Xiaoyan Wang, Lin Wu, Wenjun Xiong, Tao Chen, Guoxin Li, Zhenhui Li, Jiang Yu, Yuming Jiang
Introduction
Tumor-associated neutrophils (TAN) critically promote gastric cancer progression. However, current assessment relies on invasive biopsies that preclude serial monitoring. Noninvasive tools to quantify TAN infiltration are urgently required.
Objectives
To develop and validate a noninvasive, CT-based ensemble machine learning radiomic biomarker for mapping TAN infiltration in gastric cancer, and to assess its utility for prognosis stratification and the prediction of response to anti-PD-1 immunotherapy.
Methods
In this multicenter study of 2,170 gastric cancer patients across eight cohorts, we developed EnmlbaRB, an ensemble machine-learning-based CT radiomic biomarker. Portal venous-phase scans were processed to extract features, with mRMR-Boruta algorithms identifying 11 radiomic signatures (six peritumoral and five intratumoral signatures). These were integrated via a five-tier heterogeneous stacking architecture supervised by the immunohistochemistry-derived CD66b + TAN status (high/medium/low). The validation spanned six independent cohorts, including 177 anti-PD-1-treated patients.
Results
External validation demonstrated robust performance: EnmlbaRB predicted TAN status with an AUC of 0.71 (95%CI: 0.65–0.78) and 80.74% specificity. Critically, TAN-Low patients exhibited significantly superior 5-year overall survival compared to TAN-High across all cohorts (e.g., SYSUCC cohort: 64.12% vs. 46.78%, p < 0.05). In the anti-PD-1 cohorts, the TAN-Low subgroups achieved 1.9-fold higher disease control rates (83.9% vs 44.1%; p < 0.001) and significantly prolonged median progression-free survival (>41.9 vs 6.2 months; HR = 0.162, p < 0.001), establishing clear clinical utility for immunotherapy stratification.
Conclusions
This study is the first clinically validated noninvasive solution for mapping the TAN infiltration status in gastric cancer. EnmlbaRB effectively stratified the patients based on survival outcomes and immunotherapy responsiveness. This paradigm empowers clinicians to personalize therapeutic sequencing based on evolving TAN biology, thereby addressing the critical need for adaptive treatment strategies for advanced gastric cancer management.
肿瘤相关中性粒细胞（TAN）对胃癌的进展有重要的促进作用。然而，目前的评估依赖于侵入性活检，排除了串行监测。目前迫切需要量化TAN浸润的无创工具。目的开发和验证一种无创的、基于ct的集成机器学习放射组学生物标志物，用于胃癌中TAN的浸润，并评估其在预后分层和预测抗pd -1免疫治疗反应中的应用。在这项跨8个队列的2170名胃癌患者的多中心研究中，我们开发了EnmlbaRB，一种基于机器学习的集成CT放射组学生物标志物。门静脉期扫描被处理以提取特征，mRMR-Boruta算法识别11个放射特征（6个肿瘤周围和5个肿瘤内特征）。这些通过免疫组织化学衍生的CD66b + TAN状态（高/中/低）监督的五层异质堆叠架构进行整合。验证跨越6个独立队列，包括177名抗pd -1治疗的患者。结果外部验证表明，EnmlbaRB预测TAN状态的AUC为0.71 (95%CI: 0.65-0.78)，特异性为80.74%。关键的是，在所有队列中，TAN-Low患者的5年总生存率明显优于TAN-High患者（例如，SYSUCC队列：64.12%对46.78%,p <； 0.05）。在抗pd -1队列中，TAN-Low亚组的疾病控制率提高了1.9倍（83.9% vs 44.1%; p <； 0.001），并显著延长了中位无进展生存期（>41.9 vs 6.2个月；HR = 0.162,p <； 0.001），为免疫治疗分层建立了明确的临床应用。结论本研究是第一个经临床验证的用于胃癌中TAN浸润状态的无创检测方法。EnmlbaRB基于生存结果和免疫治疗反应性有效地对患者进行分层。这种模式使临床医生能够基于不断发展的TAN生物学来个性化治疗测序，从而解决了晚期胃癌管理中适应性治疗策略的关键需求。
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Pub Date : 2026-02-01DOI: 10.1016/j.jare.2026.01.077
Junyan Zhuang, Ye Chen, Yi Zhang, Yongrui Hai, Renming Fan, Jiarui Dou, Xintong Lu, Wenhui Wang, Bingjie Zhang, Zhuang Hou, Lei Liang, Yang Liu, Gaofei Wei
Introduction
Glutamine is a key nutrient that supports tumor cell metabolism, biosynthesis, and proliferation. It also shapes the tumor microenvironment and modulates cell death pathways. Glutamine antagonists have emerged as effective therapeutic agents by both disrupting tumor energy metabolism and enhancing antitumor immune responses. However, recent evidence reveals a paradoxical effect: glutamine deprivation can induce PD-L1 expression on tumor cells, facilitating immune escape and reducing the efficacy of immunotherapies.
Objectives
This study aims to overcome the immune evasion triggered by glutamine deprivation by developing a dual-functional therapeutic strategy that enhances metabolic stress while simultaneously inhibiting PD-L1 expression. The ultimate goal is to strengthen antitumor immunity and improve therapeutic outcomes.
Methods
We designed and synthesized a novel prodrug, HB023, by covalently linking a glutamine metabolism inhibitor with JQ1, a well-characterized PD-L1 inhibitor. We evaluated the effects of HB023 on tumor cell pyroptosis, energy metabolism, PD-L1 expression, T cell-mediated cytotoxicity, and macrophage polarization using a combination of in vitro cell-based assays and in vivo tumor models.
Results
HB023 significantly enhanced glutamine starvation in tumor cells, leading to increased pyroptosis and restricted energy supply. It effectively downregulated PD-L1 expression, which restored T cell cytotoxic activity. Additionally, HB023 induced mitochondrial membrane remodeling in macrophages, promoting M1 polarization and thereby enhancing innate immune responses. These mechanisms cooperatively activated both adaptive and innate antitumor immunity, thereby conferring HB023 with superior antitumor efficacy compared with JQ1, JHU083, or their combination.
Conclusion
HB023 successfully addresses the challenge of glutamine deprivation-induced immune escape by integrating metabolic inhibition with immune checkpoint blockade. This dual-modulatory approach reprograms the tumor immune microenvironment and improves immunotherapeutic efficacy, representing a promising strategy for advancing cancer treatment.
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Pub Date : 2026-01-30DOI: 10.1016/j.jare.2026.01.057
Jimyeong Park, Minseo Kim, Changhyun Jin, Kyu Hyoung Lee, Myung Sik Choi
{"title":"Simultaneous engineering of the surface (oxygen/amorphous carbon) and interface (amorphous carbon/ZnO) of ZnO using a one-spoon amorphous carbon deposition technique","authors":"Jimyeong Park, Minseo Kim, Changhyun Jin, Kyu Hyoung Lee, Myung Sik Choi","doi":"10.1016/j.jare.2026.01.057","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.057","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"43 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-27DOI: 10.1016/j.jare.2026.01.058
Mmi Xu, Jianwei Chen, Yi Sun, Han Yang, Hongli Ji, Tao Xu, Feng Lu, Yunfan He
Tissue engineering has become prominence in soft-tissue reconstruction. Adipogenesis and angiogenesis are important in the formation of engineering adipose tissue. Although acellular adipose matrix (AAM) possesses potential in adipogenic induction, obvious limitations remain in the realization of the authentic physiological regeneration. Matrix-bound nanovesicles (MBVs), located on the extracellular matrix (ECM) scaffold, provide cues for the adipogenesis property of AAM. The bioactive components within ECM are influenced by the isolation procedures.
{"title":"An injectable microsphere-reinforced system for sustained delivery of Adipo-MBV in adipose tissue engineering","authors":"Mmi Xu, Jianwei Chen, Yi Sun, Han Yang, Hongli Ji, Tao Xu, Feng Lu, Yunfan He","doi":"10.1016/j.jare.2026.01.058","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.058","url":null,"abstract":"Tissue engineering has become prominence in soft-tissue reconstruction. Adipogenesis and angiogenesis are important in the formation of engineering adipose tissue. Although acellular adipose matrix (AAM) possesses potential in adipogenic induction, obvious limitations remain in the realization of the authentic physiological regeneration. Matrix-bound nanovesicles (MBVs), located on the extracellular matrix (ECM) scaffold, provide cues for the adipogenesis property of AAM. The bioactive components within ECM are influenced by the isolation procedures.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"28 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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