Minimal Residual Disease, Metastasis and Immunity

Abstract

Progression from localized to metastatic disease requires cancer cells spreading to distant organs through the bloodstream. Only a small proportion of these circulating tumor cells (CTCs) survives dissemination due to anoikis, shear forces and elimination by the immune system. However, all metastases originate from CTCs capable of surviving and extravasating into distant tissue to re-initiate a tumor. Metastasis initiation is not always immediate as disseminated tumor cells (DTCs) may enter a non-dividing state of cell dormancy. Cancer dormancy is a reversible condition that can be maintained for many years without being clinically detectable. Subsequently, late disease relapses are thought to be due to cancer cells ultimately escaping from dormant state. Cancer dormancy is usually associated with minimal residual disease (MRD), where DTCs persist after intended curative therapy. Thus, MRD is commonly regarded as an indicator of poor prognosis in all cancers. In this review, we examine the current understanding of MRD and immunity during cancer progression to metastasis and discuss clinical perspectives for oncology.

Keywords: CTC; DTC; MRD; dormancy; immunity; metastasis; therapy.

Figure 1

In order to colonize distant organs, circulating cancer cells will eventually adhere and transmigrate through the endothelium thanks to the expression of different ligands and receptors. Following trans-endothelial migration, cancer cells will either enter a dormant or a proliferative state. Disseminated cancer cells’ dormancy or proliferation is determined by both intrinsic signaling and cues originating from the surrounding restrictive or permissive niche.