Abstract
Despite tremendous success against hematological malignancies, the performance of chimeric Ag receptor T cells against solid tumors remains poor. In such settings, the lack of success of this groundbreaking immunotherapy is in part mediated by ligand engagement of immune checkpoint molecules on the surface of T cells in the tumor microenvironment. Although CTLA-4 and programmed death-1 (PD-1) are well-established checkpoints that inhibit T cell activity, the engagement of glycans and glycan-binding proteins are a growing area of interest due to their immunomodulatory effects. This review discusses exemplary strategies to neutralize checkpoint molecules through an in-depth overview of genetic engineering approaches aimed at overcoming the inhibitory programmed death ligand-1 (PD-L1)/PD-1 axis in T cell therapies and summarizes current knowledge on glycoimmune interactions that mediate T cell immunosuppression.
Copyright © 2022 by The American Association of Immunologists, Inc.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Review
MeSH terms
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B7-H1 Antigen / antagonists & inhibitors*
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CTLA-4 Antigen / immunology*
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CTLA-4 Antigen / metabolism
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Cell- and Tissue-Based Therapy / methods
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Galectin 1 / immunology
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Galectin 3 / immunology
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Galectins / immunology
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Humans
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Immunomodulation / immunology
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Immunotherapy, Adoptive / methods*
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Lymphocyte Activation / immunology
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Neoplasms / immunology
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Neoplasms / therapy*
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Polysaccharides / metabolism
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Programmed Cell Death 1 Receptor / antagonists & inhibitors
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Programmed Cell Death 1 Receptor / immunology*
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Programmed Cell Death 1 Receptor / metabolism
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Receptors, Chimeric Antigen / immunology
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T-Lymphocytes / immunology
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T-Lymphocytes / transplantation*
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Tumor Microenvironment / immunology
Substances
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B7-H1 Antigen
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CD274 protein, human
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CTLA-4 Antigen
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CTLA4 protein, human
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Galectin 1
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Galectin 3
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Galectins
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LGALS9 protein, human
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PDCD1 protein, human
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Polysaccharides
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Programmed Cell Death 1 Receptor
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Receptors, Chimeric Antigen