Cancer immunotherapies, such as immune checkpoint blockade and chimeric antigen receptor (CAR) T cell therapy, have transformed clinical oncology. However, limited patient response rates and immune-related adverse events remain major clinical challenges. The immunosuppressive tumour microenvironment (TME) has a key role in the response to immunotherapy. The TME of solid tumours can prevent infiltration and negatively affect the activity of immune cells. The immunosuppressive features of the TME can be modulated using biomaterials-based tools that target, respond to and modulate the physicochemical properties of the TME, including hypoxia, acidity, high levels of reactive oxygen species, a dense extracellular matrix and abnormal vasculature. In this Review, we introduce hallmarks of the TME and discuss biomaterials and nanomedicine technologies that can regulate the TME of solid tumours to improve the efficacy of different types of immunotherapy. We outline the remaining challenges in the clinical translation of TME-modulating biomaterials tools and conclude by envisioning future milestones in this field.
The immunosuppressive tumour microenvironment (TME) has a crucial role in limiting the therapeutic responses of solid tumours to immunotherapy.
The physicochemical features of the TME, including hypoxia, acidity and high reactive oxygen species (ROS) levels, contribute to the immunosuppressive TME.
These features of the TME can be modulated by biomaterials and nanomedicine tools to make the TME susceptible to antitumour immune responses.
Combining TME-modulating biomaterials-based therapeutics with immunotherapies can improve clinical outcomes and increase patient response rates.
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This work was partially supported by the National Key Research and Development Program of China (grant 2021YFF0701800), the National Natural Science Foundation of China (grants 52032008, 32101070), the Jiangsu Social Development Project (grant BE2019658), the National Postdoctoral Program for Innovative Talents (grant BX0200230), the Suzhou Key Laboratory of Nanotechnology and Biomedicine, the Postdoctoral Research Fund of Jiangsu Province (grant 2021K093A) and the Collaborative Innovation Center of Suzhou Nano Science and Technology.
Z.L. is the founder of InnoBM Pharmaceuticals, a start-up company developing biomaterial-based pharmaceuticals to improve immunotherapies against solid tumours (http://innobm.com/). Y.C. declares no competing interests.
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Chao, Y., Liu, Z. Biomaterials tools to modulate the tumour microenvironment in immunotherapy. Nat Rev Bioeng 1, 125–138 (2023). https://doi.org/10.1038/s44222-022-00004-6
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