Back to Search
Start Over
Antibody-mediated blockade of the IL23 receptor destabilizes intratumoral regulatory T cells and enhances immunotherapy.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 5/3/2022, Vol. 119 Issue 18, p1-8, 15p
- Publication Year :
- 2022
-
Abstract
- Regulatory T cells (Treg) can impede antitumor immunity and currently represent a major obstacle to effective cancer immunotherapy. Targeting tumor-infiltrating regulatory Treg while sparing systemic Treg represents an optimal approach to this problem. Here, we provide evidence that the interleukin 23 receptor (IL23R) expressed by tumor-infiltrating Treg promotes suppressive activity. Disruption of the IL23R results in increased responsiveness of destabilized Treg to the IL12 cytokine, the production of γ-interferon, and the recruitment of CD8 T cells that inhibit tumor growth. Since the Treg destabilization pathway that is initiated by IL23R blockade is distinct and independent from the destabilization pathway coupled to glucocorticoid-induced TNFRrelated protein (GITR) activation, we examined the impact of the coordinate induction of the two destabilization pathways on antitumor immune responses. Combined GITR and IL23R antibody treatment of mice inoculated with MC38 tumors resulted in robust and synergistic antitumor responses. These findings indicate that the delineation of independent Treg destabilization pathways may allow improved approaches to the development of combination immunotherapy for cancers. [ABSTRACT FROM AUTHOR]
- Subjects :
- REGULATORY T cells
INTERLEUKIN receptors
IMMUNOTHERAPY
T cells
IMMUNE response
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 119
- Issue :
- 18
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 162445014
- Full Text :
- https://doi.org/10.1073/pnas.2200757119