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. 2022 Aug 25;13:918869. doi: 10.3389/fendo.2022.918869

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Copyright © 2022 Guizhen, Guanchang, Liwen, Huifen, Zhigang, Ranran and Zujiang

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Strategies for CAR-T cells to overcome hostile TME. Regional delivery allows CAR-T cells to reach the tumor site directly. Inducing secretion of enzymes by CAR-T (eg. heparanase) to degrade ECM and optimizing CAR-T to express chemokines/chemokines receptors appears to remarkably improve CAR-T trafficking and infiltration. Disrupting the PD-1 expression on CAR-T cells or silencing/reversing the PD-1/PD-L1 axis can augment CAR-dependent antitumor activity. And modifying CAR-T to secrete pro-inflammatory factors may be an effective strategy against the inhibitory tumor microenvironment.