Sweet Immune Checkpoint Targets to Enhance T Cell Therapy

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...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2022-01, Vol.208 (2), p.278-285
Main Authors: Derosiers, Nohelly, Aguilar, William, DeGaramo, David A, Posey, Jr, Avery D
Format: Article
Language:English
Subjects:
B7-H1 Antigen - antagonists & inhibitors
Cell- and Tissue-Based Therapy - methods
CTLA-4 Antigen - immunology
CTLA-4 Antigen - metabolism
Galectin 1 - immunology
Galectin 3 - immunology
Galectins - immunology
Humans
Immunomodulation - immunology
Immunotherapy, Adoptive - methods
Lymphocyte Activation - immunology
Neoplasms - immunology
Neoplasms - therapy
Polysaccharides - metabolism
Programmed Cell Death 1 Receptor - antagonists & inhibitors
Programmed Cell Death 1 Receptor - immunology
Programmed Cell Death 1 Receptor - metabolism
Receptors, Chimeric Antigen - immunology
T-Lymphocytes - immunology
T-Lymphocytes - transplantation
Tumor Microenvironment - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.2100706