Unraveling the Phenotype of Dormant Metastases Controlled by the Immune System

Chamorro, V.; Algarra, I.; Sanz, V.; Pulido, M.; Romero, I.; Chico, E.; Millan, M.; Escano-Maestre, M.; Linares, i.; Garcia-Lora, A. M.

doi:10.1101/2024.12.02.626440

bioRxiv · 10.1101/2024.12.02.626440

Unraveling the Phenotype of Dormant Metastases Controlled by the Immune System

Chamorro, V.·Algarra, I.·Sanz, V.·Pulido, M.·Romero, I.·Chico, E.·Millan, M.·Escano-Maestre, M.·Linares, i.·Garcia-Lora, A. M.

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Abstract

During the progression of cancer, metastatic cells frequently enter a dormant phase. The immune system plays a crucial role by restricting the growth of dormant metastases, although it cannot eradicate them. In our laboratory, we developed a preclinical mouse model of metastatic dormancy. Dormant spontaneous metastases are controlled by the immune system of wild-type mice. Depletion of the host immune system causes these metastases to awaken and progress. The elucidation of the phenotype, genes, miRNAs and immune cells involved in the phenomenon of metastatic dormancy may prove in the development of effective strategies for combating metastatic disease. Dormant Metastases are compared with Nude Metastases and Overt Metastases that have never been in dormancy. The findings of the study indicate that the dormant metastases exhibit a unique and differentiated phenotype. This is evidenced by their varied response to nutrient-restrictive conditions, chemotherapeutic agents, and cytokines in vitro. Additionally, dormant metastases display a unique pattern of gene and miRNA expression. The microenvironment of dormant metastases shows an increase in certain immune cell subpopulations. Immune-controlled dormant metastases exhibit a unique phenotype that can be exploited to discover new biomarkers, as well as to develop therapies to eradicate them or control overt metastases.

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Chamorro, V., Algarra, I., Sanz, V., Pulido, M., Romero, I., Chico, E., Millan, M., Escano-Maestre, M., Linares, i., Garcia-Lora, A. M.. 2024-12-05. Unraveling the Phenotype of Dormant Metastases Controlled by the Immune System. https://doi.org/10.1101/2024.12.02.626440

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