The roles and challenges of immunosuppressive cells in TME for CAR-T cell therapy in GBM
DOI:
https://doi.org/10.54097/296e0m78Keywords:
CAR-T; immunosuppressive cells; tumor microenvironment; glioblastoma; TAMs Tregs MDSCs.Abstract
CAR-T cell therapy has achieved remarkable success and effectiveness against hematological malignancy. However, transitions of CAR-T for solid tumor are restricted abruptly due to the tumor micro-environment. Recent studies revealed that various immune cells expressed in TME prevented T cell activation, greatly reducing the efficacy of CAR-T. At present, many clinical studies and trials have been conducted on gliomas, especially glioblastoma, demonstrating that the advantages and disadvantages of applying CAR-T in clinical practice are worth exploring. In this paper, the targets and positive effects of CAR-T for glioblastoma are discussed, as well as the negative effects of T regulatory cells, myeloid-derived suppressor cells, and tumor associated macrophages in tumor microenvironment. Simultaneously, this review also proposes a few suggestions for optimizing the CAR-T therapy for glioblastoma.
Downloads
References
LEE J H, LEE J E, KAHNG J Y, et al. Human glioblastoma arises from subventricular zone cells with low-level driver mutations. Nature, 2018, 560(7717): 243-7.
MULDER W J M, OCHANDO J, JOOSTEN L A B, et al. Therapeutic targeting of trained immunity. Nat Rev Drug Discov, 2019, 18(7): 553-66.
LABANIEH L, MACKALL C L. CAR immune cells: design principles, resistance and the next generation. Nature, 2023, 614(7949): 635-48.
LARSON R C, MAUS M V. Recent advances and discoveries in the mechanisms and functions of CAR T cells. Nat Rev Cancer, 2021, 21(3): 145-61.
KENNEDY L B, SALAMA A K S. A review of cancer immunotherapy toxicity. CA Cancer J Clin, 2020, 70(2): 86-104.
ABREU T R, FONSECA N A, GONCALVES N, et al. Current challenges and emerging opportunities of CAR-T cell therapies. J Control Release, 2020, 319: 246-61.
CHEN J, MCKAY R M, PARADA L F. Malignant glioma: lessons from genomics, mouse models, and stem cells. Cell, 2012, 149(1): 36-47.
MAJZNER R G, RAMAKRISHNA S, YEOM K W, et al. GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature, 2022, 603(7903): 934-41.
KOCKX M M, MCCLELAND M, KOEPPEN H. Microenvironmental regulation of tumour immunity and response to immunotherapy. J Pathol, 2021, 254(4): 374-83.
WU Y, YI M, NIU M, et al. Myeloid-derived suppressor cells: an emerging target for anticancer immunotherapy. Mol Cancer, 2022, 21(1): 184.
WU M, WU L, WU W, et al. Phagocytosis of Glioma Cells Enhances the Immunosuppressive Phenotype of Bone Marrow-Derived Macrophages. Cancer Res, 2023, 83(5): 771-85.
VAN DE DONK N, ZWEEGMAN S. T-cell-engaging bispecific antibodies in cancer. Lancet, 2023, 402(10396): 142-58.
MERIC-BERNSTAM F, LARKIN J, TABERNERO J, et al. Enhancing anti-tumour efficacy with immunotherapy combinations. Lancet, 2021, 397(10278): 1010-22.
Downloads
Published
Issue
Section
License
Copyright (c) 2023 Highlights in Science, Engineering and Technology
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
