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Nanosized drug delivery systems modulate the immunosuppressive microenvironment to improve cancer immunotherapy

Abstract

Immunotherapy that activates immune systems for combating cancer has yielded considerable clinical benefits recently. However, the immunosuppressive tumor microenvironment (ITME) is a major hurdle to immunotherapy as it supports tumor to evade immune surveillance. Reversing ITME facilitates the recruitment and activation of antitumor immune cells, thereby promoting immunotherapy. Our group has developed various nanosized drug delivery systems (NDDSs) to modulate ITME with enhanced efficacy and safety. In the review we introduce the ITME-remodeling strategies for improving immunotherapy based on NDDSs including triggering tumor cells to undergo immunogenetic cell death (ICD), applying tumor vaccine, and directly regulating intratumoral immune components (immune cells or cytokines). In order to guide the design of NDDSs for amplified effects of antitumor immunotherapy, the contributions and future directions of this field are also discussed.

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Fig. 1: Nanosized drug delivery systems (NDDSs) modulating the immunosuppressive tumor microenvironment (ITME).
Fig. 2: NDDS-based ICD induction for improving immunotherapy.
Fig. 3: Hydrogel containing the personalized cancer vaccine activating antitumor immune responses.
Fig. 4: PD1-overexpressing T-lymphocyte membrane-decorated nanoplatform for increasing intratumoral IFN-γ levels and blocking PD-L1.

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Acknowledgements

National Natural Science Foundation of China (81871471, 31930066, 32130058, and 32171315), Natural Science Foundation of Shanghai (19ZR1479900), Science and Technology Commission of Shanghai Municipality (19431900800), International Partnership Program of CAS (153631KYSB20190013), Natural Science Foundation of Shandong (ZR2019ZD25), Special Research Assistant Project of CAS, China Postdoctoral Science Foundation (2020M681428), and Shanghai Postdoctoral Excellence Program (2020495) are gratefully acknowledged for financial support.

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Correspondence to Qi Yin or Ya-ping Li.

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Yan, Wl., Lang, Tq., Yuan, Wh. et al. Nanosized drug delivery systems modulate the immunosuppressive microenvironment to improve cancer immunotherapy. Acta Pharmacol Sin 43, 3045–3054 (2022). https://doi.org/10.1038/s41401-022-00976-6

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  • DOI: https://doi.org/10.1038/s41401-022-00976-6

Keywords

  • immunotherapy
  • nanosized drug delivery systems (NDDSs)
  • immunosuppressive tumor microenvironment (ITME)
  • immunogenetic cell death (ICD)
  • tumor vaccine

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