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Lin et al. Cancer Drug Resist. 2026;9:14 Page 15 of 19

tumor-extrinsic immunosuppressive programs (e.g., MDSC- and macrophage-mediated suppression) that
converge on impaired T-cell priming, trafficking, and effector function.

Nanomaterial-enabled strategies provide a flexible toolkit to address these determinants by (i) modulating
resistance-associated signaling pathways; (ii) enabling localized or multivalent interception of the
PD-1/PD-L1 axis; (iii) silencing checkpoint genes using nucleic-acid delivery platforms; and (iv)
reprogramming the TME to favor productive antitumor immunity. Nevertheless, most mechanistically
matched nano-interventions remain preclinical, and translation will require biomarker-guided patient
stratification, scalable GMP-compliant manufacturing, rigorous safety evaluation, and reproducible efficacy
across clinically relevant models.

DECLARATIONS
Acknowledgments
The graphical abstract was created with BioRender.com [Created in BioRender. Lin, Y. (2026) h​t​t​p​s​:​/​/​B​i​o​R​e​n
d​e​r​.​c​o​m​/​3​5​x​a​x​5​y​].

Authors’ contributions
Wrote the manuscript: Lin Y
Supervision: Shen J

Availability of data and materials
Not applicable.

AI and AI-assisted tools statement
During the preparation of this manuscript, the AI tool ChatGPT (version 5.4, released 2026-03-05) was used
solely for language editing. The tool did not influence the study design, data collection, analysis,
interpretation, or the scientific content of the work. All authors take full responsibility for the accuracy,
integrity, and final content of the manuscript.

Financial support and sponsorship
None.

Conflicts of interest
Shen J is the Guest Editor of the special issue “Advancements in Precision Medicine for Overcoming Cancer
Drug Resistance” in the journal Cancer Drug Resistance, also serves as an Editorial Board Member of the
journal. He was not involved in any steps of editorial processing, notably including reviewers’ selection,
manuscript handling and decision making. Lin Y declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2026.

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