Post-immunotherapy CTLA-4 Ig treatment improves antitumor efficacy.
Proc Natl Acad Sci U S A
; 121(27): e2404661121, 2024 Jul 02.
Article
in En
| MEDLINE
| ID: mdl-38923991
ABSTRACT
Immune checkpoint therapies (ICT) improve overall survival of patients with cancer but may cause immune-related adverse events (irAEs) such as myocarditis. Cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA-4 Ig), an inhibitor of T cell costimulation through CD28, reverses irAEs in animal models. However, concerns exist about potentially compromising antitumor response of ICT. In mouse tumor models, we administered CTLA-4 Ig 1) concomitantly with ICT or 2) after ICT completion. Concomitant treatment reduced antitumor efficacy, while post-ICT administration improved efficacy without affecting frequency and function of CD8 T cells. The improved response was independent of the ICT used, whether CTLA-4 or PD-1 blockade. The frequency of Tregs was significantly decreased with CTLA-4 Ig. The resulting increased CD8/Treg ratio potentially underlies the enhanced efficacy of ICT followed by CTLA-4 Ig. This paradoxical mechanism shows that a CTLA-4 Ig regimen shown to reduce irAE severity does not compromise antitumor efficacy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
CTLA-4 Antigen
/
Immunotherapy
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Proc Natl Acad Sci U S A
/
Proc. Natl. Acad. Sci. U. S. A
/
Proceedings of the national academy of sciences of the United States of America
Year:
2024
Document type:
Article
Country of publication:
Estados Unidos