title: T and NK cells: two sides of tumor immunoevasion.
abstract: Natural Killer (NK) cells are known to reject several experimental murine tumors, but their antineoplastic activity in humans is not generally agreed upon, as exemplified by an interesting correspondence recently appeared in Cancer Research. In the present commentary, we join the discussion and bring to the attention of the readers of the Journal of Translational Medicine a set of recent, related reports. These studies demonstrate that effectors of the adaptive and innate immunity need to actively cooperate in order to reject tumors and, conversely, tumors protect themselves by dampening both T and NK cell responses. The recently reported ability of indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2) expressed by melanoma cells to down-regulate activating NK receptors is yet another piece of evidence supporting combined and highly effective T/NK cell disabling. Major Histocompatibility Complex class I (MHC-I) molecules, including Human Leukocyte Antigen E (HLA-E), represent another class of shared activating/inhibitory ligands. Ongoing clinical trials with small molecules interfering with IDO and PGE2 may be exploiting an immune bonus to control cancer. Conversely, failure to simultaneously engage effectors of both the innate and the adaptive immunity may contribute to explain the limited clinical efficacy of T cell-only vaccination trials. Shared (T/NK cells) natural immunosuppressants and activating/inhibitory ligands expressed by tumor cells may provide mechanistic insight into impaired gathering and function of immune effectors at the tumor site.
authors: Paediatric Haematology/Oncology Department, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant’Onofrio 4, Rome 00165, Italy.
authors: Doriana
authors: D
authors: Fruci
authors: Elisa
authors: E
authors: Lo Monaco
authors: Loredana
authors: L
authors: Cifaldi
authors: Franco
authors: F
authors: Locatelli
authors: Elisa
authors: E
authors: Tremante
authors: Maria
authors: M
authors: Benevolo
authors: Patrizio
authors: P
authors: Giacomini
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D002986:Clinical Trials as Topic; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000166:cytology*; D008024:Ligands; D008285:Major Histocompatibility Complex; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D055607:Receptors, Natural Killer Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology*; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents; D008024:Ligands; D055607:Receptors, Natural Killer Cell
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