Lessons from CTLA-4 deficiency and checkpoint inhibition

Research output: Contribution to journalReview article

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)14-19
Number of pages6
JournalCurrent Opinion in Immunology
Volume49
DOIs
Publication statusPublished - 1 Dec 2017

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this