No cancer in cancers: Evolutionary trade-off between successful viviparity and tumor escape from the adaptive immune system

Abstract

Some invertebrate species including the king crab and king squid enjoy relatively long lives of up to 20 years. Nevertheless, there are few reports of malignancies among invertebrate animals while there are many such reports in lower vertebrates such as in fishes, amphibians, and reptiles. Viviparity is characteristic of most mammalian species, although it has been observed in both vertebrate and non-vertebrate species. As adaptive immune responses evolved among the cartilaginous fishes by virtue of gene duplication, all viviparous vertebrates cope with specific immune responses to reject the fetal allograft. The escape mechanisms employed by both human and animal malignancies share common properties, which are also employed by feto-placental units, such as the expression of non-classical major histocompatibility antigens (HLA-E, HLA-F, and HLA-G in humans), accumulation of regulatory T cells, Th2-directed immune responses, Fas/FasL- and/or PD-1/PD-L1-induced apoptosis, and the expression of indoleamine 2, 3 dioxygenase which starves the local tryptophan supply that is indispensable for an effective cytotoxic T cells response. In humans, a single cancer cell requires 1-10 years to develop into a clinically remarkable tumor. For cancer cells, the genes encoding the immunoregulatory mechanisms employed by feto-placental units could be of value for escaping the host immune system. Taken together, these observations support the author's hypothesis that the evolution of viviparity resulted in an evolutionary trade-off that may have increased susceptibility to malignancies.