Human embryo immune escape mechanisms rediscovered by the tumor

• Published in: Immunobiology (1979) Vol. 214; no. 1; pp. 61 - 76
• Main Authors: Ridolfi, Laura, Petrini, Massimiliano, Fiammenghi, Laura, Riccobon, Angela, Ridolfi, Ruggero
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier GmbH 01-01-2009
• Subjects: Advanced Basic Science; Allergy and Immunology; Animals; Embryo immune escape; Embryo Research; Embryonic Development - immunology; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; HLA Antigens; Humans; Immune Tolerance; Immunity; Neoplasms - immunology; Tumor Escape; Tumor immune escape; Tumor immunosuppression; TRAIL; Tumor immune escape; human leukocyte antigen; Embryo immune escape; VEGF; Tumor immunosuppression; killer cell Ig-like inhibitory receptor; MHC; major histocompatibility complex; uterine NK; natural killer; uNK; KIR; vascular endothelial growth factor; helper-2 T lymphocyte; helper-1 T lymphocyte; TNF-related apoptosis-inducing ligand; HLA; Th1; NK; dendritic cell; DC; Th2
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2008.03.003

Abstract Towards the end of the 1990s, the two opposing theories on immunosurveillance and immunostimulation were extensively studied by researchers in an attempt to understand the complex mechanisms that regulate the relation between tumors and the host's immune system. Both theories probably have elements that would help us to comprehend how the host can induce anti-tumor clinical responses through stimulation of the immune system and which could also give us a deeper insight into the mechanisms of tumor immunosuppression. The model that most resembles the behavior of tumor cells in terms of growth, infiltration and suppression of the immune system of the environment in which they live is undoubtedly that of the embryonic cell. The fetus behaves like an allogenic transplant within the mother's body, using every means it has to escape from and defend itself against the mother's immune system. The majority of these mechanisms are the same as those found in tumor cells: antigenic loss, lack of expression of classic HLA-I molecules, production of immunosuppressive cytokines, induction of lack of expression of co-stimulatory molecules in antigen presenting cells, and induction of apoptosis in infiltrating lymphocytes, with activation of a type Th2 regulatory lymphocyte response. A careful and comparative study of key mechanisms capable of triggering tolerance or cytotoxicity in both embryonic and tumor cells could prove immensely valuable in designing new strategies for anti-tumor immunotherapy.