1. B7-H3 immunoregulatory roles in cancer.
- Author
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Mortezaee, Keywan
- Subjects
- *
T-cell exhaustion , *BISPECIFIC antibodies , *IMMUNE checkpoint inhibitors , *T cells , *MONOCLONAL antibodies - Abstract
B7 homolog 3 (B7-H3, also called CD276) is a checkpoint of B7 family that is aberrantly and consistently expressed in several human cancers, and its overexpression correlates with weak prognosis. B7-H3 is expressed on a number of cells, and it acts as a driver of immune evasion. This is mediated through hampering T cell infiltration and promoting exhaustion of CD8+ T cells. Increased B7-H3 activity also promotes macrophage polarity toward pro-tumor type 2 (M2) phenotype. In addition, high B7-H3 activity induces aberrant angiogenesis to promote hypoxia, a result of which is resistance to common immune checkpoint inhibitor (ICI) therapy. This is mediated through the impact of hypoxia on dampening CD8+ T cell recruitment into tumor area. The immunosuppressive property of B7-H3 offers insights into targeting this checkpoint as a desired approach in cancer immunotherapy. B7-H3 can be a target in blocking monoclonal antibodies (mAbs), combination therapies, chimeric antigen receptor-modified T (CAR-T) cells and bispecific antibodies. • B7-H3 is overexpressed in tumor vs. normal tissue. • B7-H3 hampers CD8+ T cell infiltration and promotes their exhaustion. • B7-H3 poorly co-expresses with PD-L1. • B7-H3 can provide an alternative mechanism for bypassing ICI therapy. • Anti-B7-H3 biAbs act more selectively compared with monotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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