A new perspective on macrophage-targeted drug research: the potential of KDELR2 in bladder cancer immunotherapy

Sep 21, 2026

Bladder cancer remains difficult to treat with limited benefits from conventional surgery, radiotherapy, and chemotherapy. This study integrates single-cell RNA sequencing and clinical data to build an RNA transcriptome map, identify candidate molecular targets, and validate antitumor activity of the lead target in vitro. Results define a tumor cell subpopulation with distinct stemness and differentiation features linked to myeloid cell interactions. KDELR2 promotes proliferation, invasion, migration, and associates with poor prognosis, immune activation, and macrophage infiltration, suggesting potential benefit from immunotherapy and macrophage-focused drug development.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages24

Reading Time1 h 0 min

AccessFree to download

Introduction

Bladder cancer burden and current treatment limits

Single-cell RNA sequencing and targeted therapy motivation

KDELR2 background and rationale

Methods

Data integration and target identification

In vitro validation

Results

Tumor subpopulation features

Myeloid signaling interactions

Functional roles of KDELR2 and prognostic associations

Discussion

Implications for immune checkpoint therapy

KDELR2 as a macrophage-focused drug target

TYPE Original Research PUBLISHED 03 December 2024 DOI 10.3389/fimmu.2024.1485109 OPEN ACCESS EDITED BY Wenyi Jin, City University of Hong Kong, China REVIEWED BY Yuquan Chen, Monash University, Australia Luo Qiang, Children ’s Hospital of Chongqing Medical University, China *CORRESPONDENCE Lingyun Liu [tmxlly@jlu.edu.cn](tmxlly@jlu.edu.cn)[ ](tmxlly@jlu.edu.cn)Yumeng Li [yingzhilifeng1995@163.com](yingzhilifeng1995@163.com)[ ](yingzhilifeng1995@163.com)Zhou Sun [sunzhou19@mails.jlu.edu.cn](sunzhou19@mails.jlu.edu.cn) †The authors have contributed equally to this work RECEIVED 23 August 2024 ACCEPTED 04 November 2024 PUBLISHED 03 December 2024 CITATION Zhao 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. Front. Immunol. 15:1485109 . doi: 10.3389/fimmu.2024.1485109 COPYRIGHT © 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. A new perspective on macrophage-targeted drug research: the potential of KDELR2 in bladder cancer immunotherapy Zhiyi Zhao 1, Hongling Jia 2, Zhou Sun 3*†, Yumeng Li 2*† and Lingyun Liu 1*† 1 Department of Andrology, The First Hospital of Jilin University, Changchun, Jilin, China, 2The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China, 3 Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China Introduction: 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. Methods: 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. Results: 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. Discussion: 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. KEYWORDS bladder cancer, S100A8, TCs, KDELR2, macrophage Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) Zhao et al. 10.3389/fimmu.2024.1485109 GRAPHICAL ABSTRACT Workﬂow 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. 1 Introduction On 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

FAQs

What treatment limitations motivated this study on bladder cancer?

The study notes that conventional surgery, radiotherapy, and chemotherapy provide largely limited patient benefits, and immunotherapy advantages are restricted in certain bladder cancer types.

How were potential molecular targets identified?

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.

What role does KDELR2 play according to the results?

KDELR2 is associated with tumor cell proliferation, invasion, and migration, correlates with poor survival, and shows links to immune activation and increased macrophage infiltration.

Sep 21, 2026

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