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Can We Use CAR-T Cells to Overcome Immunosuppression in Solid Tumours?

作者信息

Gwadera Julia, Grajewski Maksymilian, Chowaniec Hanna, Gucia Kasper, Michoń Jagoda, Mikulicz Zofia, Knast Małgorzata, Pujanek Patrycja, Tołkacz Amelia, Murawa Aleksander, Dobosz Paula

机构信息

Faculty of Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland.

Department of Patomorphology, Poznan University of Medical Sciences, 61-701 Poznan, Poland.

出版信息

Biology (Basel). 2025 Aug 12;14(8):1035. doi: 10.3390/biology14081035.


DOI:10.3390/biology14081035
PMID:40906384
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12384035/
Abstract

Chimeric antigen receptor (CAR)-T-cell therapy has revolutionised haematological cancer treatment. However, its application in solid tumours remains significantly limited by the immunosuppressive tumour microenvironment (TME), poor antigen specificity, and physical barriers to infiltration. This review explores a compelling question: can CAR-T cells be adapted to overcome immunosuppression in solid tumours effectively? We provide an in-depth analysis of the immunological, metabolic, and structural challenges posed by the TME and critically evaluate emerging engineering strategies designed to enhance CAR-T cells' persistence, targeting, and function. These include metabolic reprogramming, hypoxia-responsive constructs, checkpoint-resistant designs, and innovative delivery techniques such as locoregional administration and nanotechnology-assisted targeting. We highlight promising preclinical and early clinical studies demonstrating that armoured CAR-T cells secreting cytokines like interleukin (IL)-12 and IL-18 can reprogram the TME, restoring antitumour immunity. Moreover, we examine synergistic combination therapies that integrate CAR-T cells with immune checkpoint inhibitors, radiotherapy, oncolytic viruses, and epigenetic modulators. Special attention is given to personalised strategies, such as bispecific targeting and precision delivery to tumour-associated vasculature or stromal elements, which are showing encouraging results in overcoming resistance mechanisms. This review aims not only to synthesise current advancements but also to ignite optimism in the potential of CAR-T-cell therapy to breach the immunological fortress of solid tumours. As we enter a new era of synthetic immunology, this evolving landscape offers hope for durable remissions and novel treatment paradigms. For clinicians, researchers, and biotech innovators, this paper provides a roadmap toward transforming a therapeutic dream into clinical reality.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0f9/12384035/246bf8b9f82f/biology-14-01035-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0f9/12384035/46f111ac40e5/biology-14-01035-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0f9/12384035/5695ce15fd44/biology-14-01035-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0f9/12384035/246bf8b9f82f/biology-14-01035-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0f9/12384035/46f111ac40e5/biology-14-01035-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0f9/12384035/5695ce15fd44/biology-14-01035-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0f9/12384035/246bf8b9f82f/biology-14-01035-g003.jpg

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Can We Use CAR-T Cells to Overcome Immunosuppression in Solid Tumours?

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本文引用的文献

[1]
Extracellular matrix dynamics in tumor immunoregulation: from tumor microenvironment to immunotherapy.

J Hematol Oncol. 2025-6-19

[2]
Research progress on HER2-specific chimeric antigen receptor T cells for immunotherapy of solid tumors.

Front Immunol. 2025-5-21

[3]
Enhancing mesothelin CAR T cell therapy for pancreatic cancer with an oncolytic herpes virus boosting CAR target antigen expression.

Cancer Immunol Immunother. 2025-5-14

[4]
Angiogenesis and targeted therapy in the tumour microenvironment: From basic to clinical practice.

Clin Transl Med. 2025-4

[5]
CAR-T therapy in solid tumors.

Cancer Cell. 2025-4-14

[6]
The solid tumor microenvironment and related targeting strategies: a concise review.

Front Immunol. 2025-3-26

[7]
HER2-positive gastric cancer: from targeted therapy to CAR-T cell therapy.

Front Immunol. 2025-3-13

[8]
Brain-to-vein and vein-to-vein times and outcomes in CAR T-cell therapy in myeloma.

Blood Cancer J. 2025-3-28

[9]
Advances in bioengineered CAR T/NK cell therapy for glioblastoma: Overcoming immunosuppression and nanotechnology-based strategies for enhanced CAR T/NK cell therapy.

Bioeng Transl Med. 2024-8-31

[10]
Comprehensive Review of Early and Late Toxicities in CAR T-Cell Therapy and Bispecific Antibody Treatments for Hematologic Malignancies.

Cancers (Basel). 2025-1-17

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