One-dimensional nanosonosensitizer boosted multiple branches of immune responses against MHC-deficient immune-evasive urologic tumor

Sep 23, 2026

Cancer immunotherapies depend on CD8+ cytolytic T lymphocytes (CTLs) recognizing and eliminating tumor cells through antigens presented on MHC-I molecules. However, human and murine urologic tumors can exhibit MHC-I deficiency, reducing immunotherapy effectiveness. The study reports a one-dimensional bamboo-like multisegmented manganese dioxide@manganese–bismuth vanadate (BMMBV) nanosonosensitizer that boosts sonodynamic activity and promotes antigen spreading and adjuvant signaling, driving dendritic cell maturation and higher-aptitude CTLs. BMMBV therapy up-regulates MHC on tumor cells and, with innate immune cells, enables enhanced elimination of mouse urologic tumors.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages23

Reading Time58 min

AccessFree to download

Introduction

Immuno-oncology and clinical evolution

CTL recognition via MHC-I and limitations from MHC-I deficiency

Sonodynamic therapy and sonosensitizers

Tumor evolution toward immune-evasive MHC-I–deficient clones

CANCER One-dimensional nanosonosensitizer boosted multiple branches of immune responses against MHC-deficient immune-evasive urologic tumor Wei Yang1†, Sichen Di1†, ZihuanYang2†, Jianwei Cao1†, Qingqiao Fu3, Hongze Ren2, Hui Cheng2, Yujie Xie2, Wencong Jia2, Xinyue Dai2*, Meihua Yu2*, Yu Chen2,4,5*, Xingang Cui1* Cancer immunotherapies rely on CD8+ cytolytic T lymphocytes (CTLs) in recognition and eradication of tumor cells via antigens presented on major histocompatibility complex class I (MHC-I) molecules. However, we observe MHC-I deficiency in human and murine urologic tumors, posing daunting challenges for successful immunotherapy. We herein report an unprecedented nanosonosensitizer of one-dimensional bamboo-like multisegmented manganese dioxide@manganese–bismuth vanadate (BMMBV) to boost multiple branches of immune responses targeting MHC-I–deficient tumors. BMMBV markedly augments sonodynamic activity contributed by manganese heteroatoms in the lattice of bismuth vanadate with narrowing bandgaps. Under sonoirradiation, BMMBV enhances tumor antigen spreading and emission of adjuvant signals, which potentiate dendritic cell maturation, thereby eliciting high aptitude of CTLs. This therapy substantially up-regulates MHC expression on tumor cells, which are reversely sensitive to CTLs. Alongside, extensive innate immune cells complement the cytolytic activity of CTLs for eliminating mouse urologic tumors. This study offers a reinforced strategy against antigen-loss immune-evasive tumor. copyright © 2025 the Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. no claim to original U.S. Government Works. distributed under a creative commons Attribution noncommercial license 4.0 (cc BY-nc) . INTRODUCTION The accelerated knowledge in immuno-oncology has led to a remarkable evolution in cancer immunotherapy in clinical practice, ranging from therapeutic cancer vaccines, checkpoint blockades, and adoptive T cell transfer ( 1–3). In urologic oncology, the history of immunotherapy in treating urologic cancers dates back to 1976 when Morales and colleagues (4) first used intravesical Bacillus CalmetteGuérin after endoscopic resection to harness the immune system against invasive bladder cancers. Currently, Bacillus Calmette-Guérin remains the standard care of patients with bladder cancer. Despite the astounding improvements in treating different types of urologic cancers, including prostate, bladder, and kidney cancers, the clinical responses to immunotherapies show substantial variability, which is largely caused by the multifaceted immunological network in tumor microenvironment and heterogeneity of tumor cells (5–9) . The efficacy of cancer immunotherapies is mainly attributed to the capability of endogenous CD8+ cytolytic T lymphocytes (CTLs) or genetically engineered T cells in specifically recognizing the antigens presented on cancerous cells via major histocompatibility complex class I (MHC-I) molecules ( 10, 11) . Upon recognition, CTLs destruct cancer cells by releasing cytolytic granules and cytokines [e.g., interferon-γ (IFN-γ)]. Acting as a boost to T cell–based immunotherapies, the utility of adjunctive strategies in clinic, such as chemotherapy (12), radiotherapy (13), cryoablation (14), and highintensity focused ultrasonography (15), promotes the generation of 1department of Urology, Xinhua hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, P. R. china. 2Materdicine lab, School of life Sciences, Shanghai University, Shanghai 200444, P. R. china. 3School of Materials Science and engineering, Shanghai University, Shanghai 200444, P. R. china. 4Oujiang laboratory (Zhejiang lab for Regenerative Medicine, vision and Brain health), Wenzhou institute of Shanghai University, Wenzhou, Zhejiang 325088, P. R. china. 5Shanghai institute of Materdicine, Shanghai 200051, P. R. china. *[corresponding author. email: dxy1](corresponding au

FAQs

Why does MHC-I deficiency hinder cancer immunotherapy in urologic tumors?

MHC-I deficiency reduces antigen presentation required for CTL recognition. This weakens direct targeting of tumor cells by cytolytic T lymphocytes.

What is BMMBV and what role does it play under ultrasound?

BMMBV is a one-dimensional bamboo-like multisegmented nanosonosensitizer. Under sonoirradiation, it enhances sonodynamic activity, supporting antigen spreading and adjuvant signal emission.

How does the proposed therapy strengthen anti-tumor immunity beyond CTLs?

It up-regulates MHC expression on tumor cells to improve CTL sensitivity. In addition, extensive innate immune cells complement CTL cytolytic activity for tumor elimination.

Sep 23, 2026

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