Exercise-induced engagement of the IL-15/IL-15Rα axis promotes anti-tumor immunity in pancreatic cancer.
Cancer Cell
; 40(7): 720-737.e5, 2022 07 11.
Article
em En
| MEDLINE
| ID: mdl-35660135
ABSTRACT
Aerobic exercise is associated with decreased cancer incidence and cancer-associated mortality. However, little is known about the effects of exercise on pancreatic ductal adenocarcinoma (PDA), a disease for which current therapeutic options are limited. Herein, we show that aerobic exercise reduces PDA tumor growth, by modulating systemic and intra-tumoral immunity. Mechanistically, exercise promotes immune mobilization and accumulation of tumor-infiltrating IL15Rα+ CD8 T cells, which are responsible for the tumor-protective effects. In clinical samples, an exercise-dependent increase of intra-tumoral CD8 T cells is also observed. Underscoring the translational potential of the interleukin (IL)-15/IL-15Rα axis, IL-15 super-agonist (NIZ985) treatment attenuates tumor growth, prolongs survival, and enhances sensitivity to chemotherapy. Finally, exercise or NIZ985 both sensitize pancreatic tumors to αPD-1, with improved anti-tumor and survival benefits. Collectively, our findings highlight the therapeutic potential of an exercise-oncology axis and identify IL-15 activation as a promising treatment strategy for this deadly disease.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Carcinoma Ductal Pancreático
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Receptores de Interleucina-15
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article