Cell-in-Cell Structures in Gastrointestinal Tumors: Biological Relevance and Clinical Applications

This review summarizes information about cell-in-cell (CIC) structures with a focus on gastrointestinal tumors. The phenomenon when one cell lives in another one has attracted an attention of researchers over the past decades. We briefly discuss types of CIC structures and mechanisms of its formation, as well as the biological basis and consequences of the cell-engulfing process. Numerous clinico-histopathological studies demonstrate the significance of these structures as prognostic factors, mainly correlated with negative prognosis. The presence of CIC structures has been identified in all gastrointestinal tumors. However, the majority of studies concern pancreatic cancer. In this field, in addition to the assessment of the prognostic markers, the attempts to manipulate the ability of cells to form CISs have been done in order to stimulate the death of the inner cell. Number of CIC structures also correlates with genetic features for some gastrointestinal tu-mors. The role of CIC structures in the responses of tumors to therapies, both chemotherapy and immunotherapy, seems to be the most poorly studied. However, there is some evidence of involvement of CIC structures in treatment failure. Here, we summarized the current literature on CIC structures in cancer with a focus on gastrointestinal tumors and specified future perspectives for investigation.