Micrometastasis as a distinct immunobiological state and therapeutic target

Metastasis is an inefficient cellular process in which most disseminated tumor cells fail to form secondary lesions in distant tissues due to hostile conditions, such as protective immune surveillance. The few cells that survive these threats can seed subclinical metastatic lesions, known as micrometastases, which are the least-known stage of the metastatic cascade. In this study, we review micrometastasis immunobiology, which differs from that of larger, clinically manifested metastasis. Key mechanisms such as epithelial-to-mesenchymal transition, stemness, dormancy, and immune evasion shape this bottleneck of metastasis, determining long-term disease evolution, therapy responses, and patient outcomes. Understanding micrometastasis immunology may reveal therapeutic opportunities to fully eradicate disseminated cells. Thus, we discuss emerging time-tailored immunopreventive strategies to intercept the progression to overt metastasis.