Impact of tumour microenvironment and Fc receptors on the activity of immunomodulatory antibodies

Highlights • FcγRs play a key role in the activity of immunomodulatory mAbs in mouse models. • αCTLA-4 expands Teff cells while selectively depleting intratumoural Treg cells. • CTLA-4 density, mAb isotype, and FcγR-expressing myeloid cells dictate outcome. • This mechanism appears common to the act...

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Veröffentlicht in:	Trends in immunology 2014-07, Vol.35 (7), p.290-298
Hauptverfasser:	Furness, Andrew J.S, Vargas, Frederick Arce, Peggs, Karl S, Quezada, Sergio A
Format:	Artikel
Sprache:	eng
Schlagworte:	Allergy and Immunology Animals anti-CTLA-4 Antibodies - immunology Antibody-Dependent Cell Cytotoxicity Antigens, Differentiation - immunology Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biomedical research Cancer Clinical trials CTLA-4 Antigen - immunology Drug Discovery Drug Synergism Fc gamma receptors Glucocorticoid-Induced TNFR-Related Protein - immunology Humans Immune system Immunomodulation immunomodulatory therapy Lymphocytes Medical research Melanoma Neoplasms - immunology Neoplasms - therapy Receptors, Fc - immunology Signal transduction T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - immunology Tumor Microenvironment tumour microenvironment
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Zusammenfassung:	Highlights • FcγRs play a key role in the activity of immunomodulatory mAbs in mouse models. • αCTLA-4 expands Teff cells while selectively depleting intratumoural Treg cells. • CTLA-4 density, mAb isotype, and FcγR-expressing myeloid cells dictate outcome. • This mechanism appears common to the activity of other immune modulatory mAb. • Translational studies in a human population are paramount.
ISSN:	1471-4906 1471-4981
DOI:	10.1016/j.it.2014.05.002