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The term “cell-in-cell” refers to a phenomenon in which one or more living cell enters into another cell,forming cell-in-cell structures,which phenomena was observed more than 100 years ago,yet their biological significance has been near-to-completely disregarded since.Cell-in-cell structure represents an evolutionarily conserved phenomenon,which can be observed not only in vertebrates but also in lower organisms,such as the cellular slime mold Dictyostelium and the worm Caenorhabditis elegans.In addition to extensive involvements in pathological processes like tumorigenesis,cell-in-cell formation also plays essential roles in biological processes,such as development of immune and reproductive system,and immune-homeostasis and the like.It has attracted great interests as it can be found across a wide range of species and attributes a biological significance in specific pathophysiological conditions.Up to date,three molecularly distinct modes of cell-in-cell death mechanisms,including entosis,emperitosis and cannibalism,had been evolved from cell-in-cell studies during past several years,some of which,such as entosis,had been included into the recommendation of the Nomenclature Committee on Cell Death 2012.This conceptual advance greatly speeds up the cell-in-cell field.We believe that more clinicians will be attracted to dedicate in the study of clinical relevance to cell-in-cell,which will integrate cell-in-cell into translational medicine and eventually leads to the identification of new therapeutic targets for human diseases.