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Overcoming physical stromal barriers to cancer immunotherapy

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Abstract

Immunotherapy has emerged as an unprecedented hope for the treatment of notoriously refractory cancers. Numerous investigational drugs and immunotherapy-including combination regimens are under preclinical and clinical investigation. However, only a small patient subpopulation across different types of cancer responds to the therapy due to the presence of several mechanisms of resistance. There have been extensive efforts to overcome this limitation and to expand the patient population that could be benefited by this state-of-the-art therapeutic modality. Among various causes of the resistance, we here focus on physical stromal barriers that impede the access of immunotherapeutic drug molecules and/or native and engineered immune cells to cancer tissues and cells. Two primary stromal barriers that contribute to the resistance include aberrant tumor vasculatures and excessive extracellular matrix build-ups that restrict extravasation and infiltration, respectively, of molecular and cellular immunotherapeutic agents into tumor tissues. Here, we review the features of these barriers that limit the efficacy of immunotherapy and discuss recent advances that could potentially help immunotherapy overcome the barriers and improve therapeutic outcomes.

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Acknowledgements

Funding was provided by the National Institute of Health (R01NS111102 and R01NS119609). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The graphical abstract was created with BioRender.

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  1. Center for Nanomedicine, The Johns Hopkins University School of Medicine, 400 N. Broadway, Baltimore, MD, 602921231, USA

    Seung Woo Chung, Yunxuan Xie & Jung Soo Suk

  2. Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA

    Seung Woo Chung, Yunxuan Xie & Jung Soo Suk

  3. Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, 21218, USA

    Yunxuan Xie & Jung Soo Suk

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Chung, S.W., Xie, Y. & Suk, J.S. Overcoming physical stromal barriers to cancer immunotherapy. Drug Deliv. and Transl. Res. 11, 2430–2447 (2021). https://doi.org/10.1007/s13346-021-01036-y

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