Year-end Sale % OFF 
Abstract
Although psycho-social stress is a well-known factor that contributes to the development of cancer, it remains largely unclear whether and how environmental eustress influences malignant diseases and regulates cancer-related therapeutic responses. Using an established eustress model, we demonstrate that mice living in an enriched environment (EE) are protected from carcinogen-induced liver neoplasia and transplantable syngeneic liver tumors, owning to a CD8+ T cell-dependent tumor control. We identify a peripheral Neuro-Endocrine-Immune pathway in eustress, including Sympathetic nervous system (SNS)/β-adrenergic receptors (β-ARs)/CCL2 that relieves tumor immunosuppression and overcomes PD-L1 resistance to immunotherapy. Notably, EE activates peripheral SNS and β-ARs signaling in tumor cells and tumor infiltrated myeloid cells, leading to suppression of CCL2 expression and activation of anti-tumor immunity. Either blockade of CCL2/CCR2 or β-AR signaling in EE mice lose the tumor protection capability. Our study reveales that environmental eustress via EE stimulates anti-tumor immunity, resulting in more efficient tumor control and a better outcome of immunotherapy.
Highlights
Psycho-social stress is a well-known factor that contributes to the development of cancer, it remains largely unclear whether and how environmental eustress influences malignant diseases and regulates cancer-related therapeutic responses
To investigate the potential protective role of eustress on liver malignant progression, we took advantage of three carcinogen- or diet-induced liver neoplasia mouse models, including diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) model, DEN and high-fat diet (HFD) model, CCl4 model and three transplantable murine liver tumors mouse models (Hepa[1,2,3,4,5,6], LPC-H12, H22) that were housed in a standard environment (SE) or EE
It is noteworthy that EE housing reduced serum AST and ALT (Supplementary Fig. 1A, B), pathological markers associated with the consequence of chronic liver injury
Summary
Psycho-social stress is a well-known factor that contributes to the development of cancer, it remains largely unclear whether and how environmental eustress influences malignant diseases and regulates cancer-related therapeutic responses. From a clinical point of view, a better understanding of how stress (distress and eustress) alters hepatic diseases would provide additional tools for treating patients with liver diseases It would improve the quality of life in patients by optimizing hospitalization conditions and ensure a more efficient therapeutic approach. It has been demonstrated that EE results in a series of beneficial effects that make the mice “happier”, reduces anxiety[19], as well as improves the symptoms of neurodegenerative diseases[20] and cancers[16,17] It requires further investigation and interrogation on whether and how eustress influences liver cancer and cancer-related therapeutic responses
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
