Antibody-mediated blockade of the IL23 receptor destabilizes intratumoral regulatory T cells and enhances immunotherapy
Abstract
Regulatory T cells rely on active processes to maintain a suppressive phenotype inside a tumor, leading to increased tumor burden and worse cancer outcomes. Here, we report a pathway to interfere with regulatory T cell (Treg) stability by disrupting the expression of the interleukin 23 receptor. This approach increases Treg responsiveness to interleukin 12, leading to increased production of gamma-interferon and more efficient antitumor immune responses. The combined engagement of independent pathways to destabilize Treg through the interleukin 23 receptor and the glucocorticoid-induced TNFR-related protein receptor has a synergistic impact on the Treg phenotype and promotes antitumor immune responses. These findings expand our understanding of regulatory T-cell biology and offer tools for cancer immunotherapy.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 28, 2022
- Source ID
- 10.1073/pnas.2200757119
Entities
People
- Andrew E. Wight
- Harvey Cantor
- Hidetoshi Nakagawa
- Hye-jung Kim
- Jessica M. Sido
- Lin Ao
- Oba Oseghali
- Sandrine Degryse
- Xianli Shen
- Yiguo Qiu(vivian)
Organizations
- American Association of Immunologists
- Cancer Research Institute
- Dana–Farber Cancer Institute
- Harvard Medical School
- National Institute of Allergy and Infectious Diseases
- United States Army Materiel Command