<p>Immune surveillance plays a pivotal role in controlling tumor emergence, dormancy and progression, including in breast cancer. Despite its potential clinical relevance, the mechanisms governing dormancy initiation, maintenance and escape, as well as the molecular mediators involved, remain poorly understood. Here, we identify the interferon-inducible chemokine CXCL10 and its receptor CXCR3 as key regulators of immunological dormancy in triple-negative breast cancer (TNBC). By transcriptomic profiling, we observed high expression of <i>Cxcl10</i> in dormant cells in two different orthotopic, syngeneic models of breast cancer dormancy (D2.0R and 4T1-MR20). Genetic silencing of <i>Cxcl10</i> in dormant cells or pharmacological blockade of CXCR3 in vivo led to early tumor onset and rapid growth in immunocompetent mice. In contrast, dormant cells effectively formed tumors in immune-deficient mice independently of <i>Cxcl10</i> status, demonstrating that the CXCL10/CXCR3 axis-mediated dormancy requires a functional immune system. Further analysis confirmed that <i>Cxcl10</i> silencing altered the local immune microenvironment, reducing CD4⁺ and CD8⁺ T cell infiltration while increasing the presence of granulocytic Myeloid Derived Suppressor Cells and Natural Killer cells. Moreover, <i>Cxcl10</i> silencing significantly increased the burden of tumor cells disseminated to the lung. Leveraging these findings, we identified a CXCL10-mediated dormancy signature that predicts improved overall survival in TNBC patients. Our findings have identified a new mechanism modulating breast cancer dormancy with two important clinical implications: the CXCL10/CXCR3 axis as a potential therapeutic target for improving survival of patients with TNBC, and the CXCL10-dependent dormancy signature as a tool for identifying these patients.</p>