Dormant Metastases Exhibit a Unique Phenotype Primarily Promoted by the Ch25h Gene and Are Maintained in Dormancy by T Lymphocytes

Abstract

During the course of cancer, metastatic cells frequently enter a state of dormancy that can be controlled by the immune system. In our laboratory, we developed a preclinical mouse model of metastatic immunodormancy. 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. 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. Furthermore, dormant metastases exhibit a distinctive transcriptional pattern of gene expression, which is predominantly promoted by the Ch25h gene. Additionally, the analysis revealed differential expression of microRNAs, with elevated levels of mir-142-3p being expressed de novo. The microenvironment of dormant metastases shows an increase in T lymphocytes (cytotoxic and helper T lymphocytes and γδ T cells) and neutrophils. 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.

Keywords

dormant metastases / antitumor immunity / gene expression / chemokines / biomarkers / ch25h / t lymphocytes / immune microenvironment

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