The role of tumor microenvironment in regulating tumor cell dormancy

Metastasis and recurrence are the major causes of tumor-related deaths which occur years after primary tumor treatment. This phenomenon can be partially attributed to dormant tumor cells which evade therapeutic interventions and survive in the body for decades without clinical detection. The tumor microenvironment (TME) is a critical regulator of this process, intricately controlling tumor cell dormancy through the integration of diverse cues from physical structures, soluble factors, metabolic conditions, and immune status. In this review, we systematically discuss how the TME governs the entry, maintenance, and reactivation of dormant tumor cells. By integrating recent advances and addressing current limitations, we aim to provide novel insights for both mechanistic studies and therapeutic strategies aimed at inducing persistent dormancy or eradicating dormant cells to prevent tumor recurrence and metastasis.