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Curr Opin Immunol. 2017 Dec;49:14-19. doi: 10.1016/j.coi.2017.07.014. Epub 2017 Aug 11.

Lessons from CTLA-4 deficiency and checkpoint inhibition.

Author information

1
Division of Translational Medicine, Research Branch, Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar. Electronic address: blo@sidra.org.
2
Division of Translational Medicine, Research Branch, Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar.

Abstract

CTLA-4 is a crucial negative regulator of immune responses. Absence of CTLA-4 in mice causes autoimmunity and lethal multiorgan lymphocytic infiltration and tissue destruction. Recently, heterozygous CTLA4 or biallelic LRBA mutations leading to functional CTLA-4 deficiency and autoimmunity have been discovered. LRBA was identified as a novel regulator of steady-state CTLA-4 protein levels in Tregs and activated T cells. CTLA-4 deficiency due to checkpoint blockade cancer immunotherapy has also been found to lead to autoimmune reactions. Studies investigating the variable efficacy and adverse autoimmune responses to checkpoint therapy elucidated a role of the microbiota in promoting antitumor and autoreactive immune responses that are regulated by CTLA-4.

PMID:
28806575
DOI:
10.1016/j.coi.2017.07.014
[Indexed for MEDLINE]

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