Lessons from CTLA-4 deficiency and checkpoint inhibition.

Lessons from CTLA-4 deficiency and checkpoint inhibition. Curr Opin Immunol. 2017 Aug 11;49:14-19 Authors: Lo B, Abdel-Motal UM 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 [PubMed - as supplied by publisher]
Source: Current Opinion in Immunology - Category: Allergy & Immunology Authors: Tags: Curr Opin Immunol Source Type: research