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

TL;DR

Dormant cancer metastases have a unique gene-driven immune-controlled state that could lead to new treatments.

Contribution

The study identifies a unique dormant metastasis phenotype primarily driven by the Ch25h gene and immune cell interactions.

Findings

Dormant metastases show a distinct response to nutrients, chemotherapy, and cytokines.

Ch25h gene expression and elevated mir-142-3p microRNA are key features of dormant metastases.

T lymphocytes and neutrophils are enriched in the microenvironment of dormant metastases.

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.

Significance: Immune‐controlled dormant metastases exhibit a unique phenotype, primarily promoted by the Ch25h gene, that can be exploited to discover new biomarkers, as well as the development of therapies to eradicate dormant metastases or control overt metastases.

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