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Targeting Myeloid Checkpoint Molecules in Combination With Antibody Therapy: A Novel Anti-Cancer Strategy With IgA Antibodies?

Journal

FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.932155

Keywords

IgA; myeloid checkpoints; neutrophils (PMNs); cancer immonotherapy; immune checkpoint; antibodies; CD47-SIRPalpha axis; macrophages

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The expression of checkpoint molecules by tumor cells hampers the clinical responses to therapeutic antibodies. Myeloid checkpoint inhibition in combination with IgA-based treatment could significantly enhance IgA therapy.
Immunotherapy with therapeutic antibodies has shown a lack of durable responses in some patients due to resistance mechanisms. Checkpoint molecules expressed by tumor cells have a deleterious impact on clinical responses to therapeutic antibodies. Myeloid checkpoints, which negatively regulate macrophage and neutrophil anti-tumor responses, are a novel type of checkpoint molecule. Myeloid checkpoint inhibition is currently being studied in combination with IgG-based immunotherapy. In contrast, the combination with IgA-based treatment has received minimal attention. IgA antibodies have been demonstrated to more effectively attract and activate neutrophils than their IgG counterparts. Therefore, myeloid checkpoint inhibition could be an interesting addition to IgA treatment and has the potential to significantly enhance IgA therapy.

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