Circadian desynchronization promotes tumor immune microenvironment remodeling favoring tumor cell proliferation

IGNACIO AIELLO; CARLOS S CALDART VALLE; DIEGO A GOLOMBEK; FERNANDA ROMÁN; JUAN JOSE CHIESA; NATALIA PALADINO; MALENA L MUL FEDELE; LUCIANO MARPEGAN; CARLA FINKIELSTEIN

Colonia del Sacramento

Congreso; XV Latin American Symposium of Chronobiology (LASC 2019); 2019

Circadian desynchronization promotes tumor immune microenvironment remodeling favoring tumor cell proliferation No programado 2h Hotel El MiradorPoster Poster session 2 (drinks and snacks)Ponente Ignacio Aiello (Laboratorio de Cronobiología, Universidad Nacional de Quilmes, Buenos Aires, Argentina)DescripciónCircadian disruption by shift work and jet-lag has been established as a health hazard both in humans and animal models. The aim of this study was to analyze the tumor growth in mice under chronic jet lag (CJL, 6 hours advances of the LD cycle every two days), using a melanoma model induced by a subcutaneous injection of the murine B16 cell line. We found an increased tumor growth rate and a decreased latency compared to normal light-dark (LD) conditions. Next, we analyzed the immune response and we found a daily pattern in the percentage of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages both in the spleen and in the tumor, and in the pro-inflammatory cytokine levels in the tumors. Under the CJL conditions, daily patterns of macrophages M1 and M2 and cytokine levels were lost or inverted. Additionally, this schedule induced the loss of rhythmic expression of the clock genes Cry1 and Bmal1, the cell-cycle inhibitor p21WAF/CIP1 and the deregulation of cyclins genes in the liver, while CcnA2 levels increased in the tumor. In summary, the increased tumor growth rate observed under CJL is associated with a circadian deregulation in the immune system and in the clock and cell cycle-related molecules.