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\nCity University of Hong Kong, China  \nREVIEWED BY  \nYuquan Chen,  \nMonash University, Australia Luo Qiang,  \nChildren ’s Hospital of Chongqing Medical University, China  \n*CORRESPONDENCE  \nLingyun Liu  \n [tmxlly@jlu.edu.cn](tmxlly@jlu.edu.cn)[ ](tmxlly@jlu.edu.cn)Yumeng Li  \n [yingzhilifeng1995@163.com](yingzhilifeng1995@163.com)[ ](yingzhilifeng1995@163.com)Zhou Sun  \n [sunzhou19@mails.jlu.edu.cn](sunzhou19@mails.jlu.edu.cn)  \n†The authors have contributed equally to this work  \nRECEIVED 23 August 2024  \nACCEPTED 04 November 2024  \nPUBLISHED 03 December 2024  \nCITATION  \nZhao Z, Jia H, Sun Z, Li Y and Liu L (2024) Anew perspective on macrophage-targeted drug research: the potential of KDELR2 in bladder cancer immunotherapy.  \nFront. Immunol. 15:1485109 .  \ndoi: 10.3389/fimmu.2024.1485109  \nCOPYRIGHT  \n© 2024 Zhao, Jia, Sun, Li and Liu. 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.  \nA new perspective on macrophage-targeted drug research: the potential of KDELR2 in bladder cancer immunotherapy  \nZhiyi Zhao 1, Hongling Jia 2, Zhou Sun 3*†, Yumeng Li 2*† and Lingyun Liu 1*†  \n1 Department of Andrology, The First Hospital of Jilin University, Changchun, Jilin, China, 2The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan,  \nShandong, China, 3 Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China  \nIntroduction: Bladder cancer was recognized as one of the most common malignant tumors in the urinary system, and treatment options remained largely limited to conventional surgery, radiotherapy, and chemotherapy, which limited patient benefits.  \nMethods: Researchers constructed an RNA transcriptome map of bladder cancer by integrating single-cell RNA sequencing and clinical data, identifying potential molecular targets for diagnosis and treatment. We also verified the antitumor activity of the target through in vitro experiment.  \nResults: A distinct tumor cell subpopulation characterized by elevated S100A8 expression exhibited high copy number variation, high stemness, and low differentiation. It interacted with myeloid cells via the MIF-(CD74+CD44) and MIF-(CD74+CXCR4) signaling pathways. This study underscored KDELR2’s role in promoting cell proliferation, invasion, and migration, providing new therapeutic insights. Prognostic analysis revealed that KDELR2 correlated with poor survival, higher immune scores, and increased macrophage infiltration.  \nDiscussion: The findings suggested that patients with high KDELR2 expression might benefit from immune checkpoint therapy. KDELR2 was also shown to enhance bladder cancer cell proliferation, invasion, and migration, highlighting itas a promising target for macrophage-focused drug development.  \nKEYWORDS  \nbladder cancer, S100A8, TCs, KDELR2, macrophage  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \nZhao et al. 10.3389/fimmu.2024.1485109  \nGRAPHICAL ABSTRACT  \nWorkflow diagram of this study. Workflow showed bladder cancer single-cell RNA sequencing data were used to perform cell stemness, pseudotime, and cell communication analyses, leading to the identification of a cell subpopulation and the creation of a prognostic model. The KDELR2 gene was validated by in vitro experiments.  \n1 Introduction  \nOn a global scale, bladder cancer holds the second position among urological malignancies in terms of prevalence, while it ranks ninth among all malignancies and stands as the 13th leadin","cbCailfIOZVF5TBL","https://ap.wps.com/l/cbCailfIOZVF5TBL","pdf",22583527,24,"English","# Introduction\n## Bladder cancer burden and current treatment limits\n## Single-cell RNA sequencing and targeted therapy motivation\n## KDELR2 background and rationale\n# Methods\n## Data integration and target identification\n## In vitro validation\n# Results\n## Tumor subpopulation features\n## Myeloid signaling interactions\n## Functional roles of KDELR2 and prognostic associations\n# Discussion\n## Implications for immune checkpoint therapy\n## KDELR2 as a macrophage-focused drug target","[{\"question\":\"What treatment limitations motivated this study on bladder cancer?\",\"answer\":\"The study notes that conventional surgery, radiotherapy, and chemotherapy provide largely limited patient benefits, and immunotherapy advantages are restricted in certain bladder cancer types.\"},{\"question\":\"How were potential molecular targets identified?\",\"answer\":\"Researchers constructed an RNA transcriptome map by integrating single-cell RNA sequencing with clinical data to identify molecular targets, followed by in vitro verification of antitumor activity.\"},{\"question\":\"What role does KDELR2 play according to the results?\",\"answer\":\"KDELR2 is associated with tumor cell proliferation, invasion, and migration, correlates with poor survival, and shows links to immune activation and increased macrophage infiltration.\"}]","A new perspective on macrophage-targeted drug research: the potential of KDELR2 in bladder cancer immunotherapy | PDF",1790017967]