Selective targeting of IL2Rßγ combined with radiotherapy triggers CD8- and NK-mediated immunity, abrogating metastasis in HNSCC.
Cell Rep Med
; 4(8): 101150, 2023 08 15.
Article
de En
| MEDLINE
| ID: mdl-37586327
ABSTRACT
The implementation of cancer immunotherapies has seen limited clinical success in head and neck squamous cell carcinoma (HNSCC). Interleukin-2 (IL-2), which modulates the survival and functionality of lymphocytes, is an attractive target for new immunotherapies but one that is limited by presence of regulatory T cells (Tregs) expressing the high-affinity IL-2Rα. The bispecific immunocytokine PD1-IL2v preferentially delivers IL-2 signaling through IL-2Rßγ on PD-1-expressing cells. Selectively targeting the intermediate-affinity IL-2Rßγ can be leveraged to induce anti-tumor immune responses in effector T cells and natural killer (NK) cells while limiting the negative regulation of IL-2Rα activation on Tregs. Using radiation therapy (RT) in combination with PD1-IL2v improves local tumor control and survival, and controls metastatic spread in orthotopic HNSCC tumor models. PD1-IL2v drives systemic activation and expansion of circulating and tumor-infiltrating cytotoxic T cells and NK cells while limiting Treg-mediated immunosuppression. These data show that PD1-L2v induces durable systemic tumor control in HNSCC.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Interleukine-2
/
Tumeurs de la tête et du cou
Type d'étude:
Prognostic_studies
Limites:
Humans
Langue:
En
Journal:
Cell Rep Med
Année:
2023
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique