061 | The circadian system modulates tumor progression: role of immune response and tumor microenvironment


Author: Guido Hokama | Email: guidohokama98@gmail.com

Guido Hokama , Ignacio Aiello , Camila Senna , Diego Golombek , Natalia Paladino

1° Laboratorio de Cronobiología, Universidad Nacional de Quilmes, Bernal, Argentina
2° Laboratorio Interdisciplinario del Tiempo (LITERA), Universidad de San Andrés, Victoria, Argentina

Most physiological and behavioral functions exhibit daily rhythms synchronized with the environmental light-dark (LD) cycle. Shift work and night work desynchronize biological rhythms, including those of the immune system, promoting the development of cancer. Previously, we reported in a non-metastatic murine melanoma model that circadian desynchronization (CJL, 6-hour advance of the LD cycle every 2 days) increases tumor growth rate and disrupts the daily patterns of M1 (anti-tumoral) and M2 (pro-tumoral) macrophages. Here, we observed that CJL induces an increase in the percentage of animals with lung metastases, as well as in the number of metastatic foci. In addition, we found a daily pattern in lung macrophage levels under LD: M1 macrophages exhibited higher levels at the end of the night and the beginning of the day, while M2 macrophages showed elevated levels at the beginning of the night. Additionally, CJL abolishes these patterns. On the other hand, we assessed the role of the tumor microenvironment: conditioned media obtained from tumors extracted at different time points induce tumor cell proliferation and migration, as well as differentiation of M0 macrophages into M1/M2, in a time-dependent way based on the tumor extraction time. These findings demonstrate that circadian desynchronization promotes metastasis formation. Moreover, this fact could depend on immune response dysregulation, which in turn could be modulated by the tumor microenvironment.