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.

Biophysics involved in the process of tumor immune escape

“…For example, with the help of neutrophils, the extravasation efficiency of melanoma increased by 85%, and it can be colonized under the shear stress of 4 dyn/cm 2 ( Slattery and Dong 2003 ). Overall, this may mean that high shear force contributes to the malignant phenotype of tumor cells, but the colonization of tumor cells from the vascular system is because of low shear force ( Badia-Ramentol et al., 2021 ). In addition, the mystery of the relationship between the action of shear stress and the protein will be gradually unraveled.…”

Tumor Dormancy: Implications for Invasion and Metastasis

“…Cancer cells might invade surrounding tissues, mostly in groups of cells, the leading front of which has the potential to release proteases and invade [ 19 ]. Upon intravasation into the bloodstream, the cells, now termed circulating tumor cells (CTCs) encounter the environmental hazards posed by the circulatory and the immune system, however, a fraction of them either individually or in clusters, surpass the risk, for instance by interacting with platelets [ 20 ]. Eventually, the adhesion of CTCs to endothelial cells is the first step of the extravasation.…”

“…Eventually, the adhesion of CTCs to endothelial cells is the first step of the extravasation. Subsequent to trans-endothelial migration, cancer cells will either enter a dormant or a proliferative state [ 20 , 21 ].…”

“…The immune system plays a key role in the maintenance of tumor dormancy [ 5 , 20 ]. An indirect indication of its role is the increased density of immune cells that have been observed in the bone marrow of patients with breast cancer displaying dormant DTCs [ 69 ].…”

Continuous sensing of IFNα by hepatic endothelial cells shapes a vascular antimetastatic barrier

“…Accordingly, there is growing recognition that the use of perioperative immunotherapies in CRC patients undergoing surgical resection may represent a unique treatment window to prevent metastatic colonization and control minimal residual disease (Badia-Ramentol et al , 2021; Bakos et al , 2018; Horowitz et al , 2015). In this context, interferon-alpha (IFNα), a pleiotropic cytokine with multiple antitumor effects such as the direct inhibition of cancer cell growth and angiogenesis (Indraccolo, 2010), the sustained upregulation of major histocompatibility complexes (Gessani et al , 2014) and the induction of innate and adaptive antitumor immune responses (Aichele et al , 2006; Curtsinger et al , 2007; Fuertes et al , 2013), has been used as adjuvant immunotherapy in various solid cancers such as renal cell carcinoma (Flanigan et al , 2001), melanoma (Lens & Dawes, 2002) and colorectal cancer (Kohne et al , 1997; Link et al , 2005).…”