OX40 agonist tumor immunotherapy does not impact regulatory T cell suppressive function

Fanny Polesso, Minhaz Sarker, Andrew D. Weinberg, Susan E. Murray, Amy E. Moran

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

OX40 is a costimulatory molecule from the TNFR family. In mice, it is expressed on Foxp3+ regulatory T cells (Tregs) constitutively and on conventional CD4 (Tconv) and CD8 T cells after Ag encounter. OX40 agonists are in clinical development to enhance antitumor immune responses, and one proposed mechanism of action is loss of Treg suppressive function. Studies have postulated that agonist OX40 therapy can impair Treg suppressive function. Using tools developed since the initial studies were published, we evaluated a direct effect of OX40 agonism on Treg function. We conclude that OX40 agonist Abs do not intrinsically impair Treg function but rather enhance Tconv cell IL-2 production, increasing Treg and Tconv cell proliferation. OX40-stimulated Tregs retain suppressive function, but also gain IFN-g, TNF-a, and granzyme B expression. These data help resolve mechanistic questions regarding OX40 agonist immunotherapy and thus are relevant to developing combination therapies that target distinct T cell functions.

Original languageEnglish (US)
Pages (from-to)2011-2019
Number of pages9
JournalJournal of Immunology
Volume203
Issue number7
DOIs
Publication statusPublished - Oct 1 2019

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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