title: Effective tumor immunotherapy: start the engine, release the brakes, step on the gas pedal,...and get ready to face autoimmunity.
abstract: Cellular immune responses can destroy cancer cells, achieving the cure of experimental malignancies. An expanding wealth of knowledge on the molecular basis of how to prime and amplify a T cell response has fueled a number of strategies successful at treating established tumors (rather than merely preventing tumor grafting). The most efficacious approaches operate at different stages, including: 1) priming the immune response using tumor antigen-expressing dendritic cells or tumor cells transfected with genes that render them immunogenic, 2) sustaining and amplifying immunity using agonistic monoclonal antibodies against costimulatory molecules or immune-potentiating cytokines, and 3) eliminating mechanisms that self-regulate the strength of the immune response, such as inhibitory receptors or regulatory T cells. A rational combination of such approaches holds great hope for cumulative and synergistic effects, but there is also evidence that they can open the flood-gates for unwanted inflammatory reactions. The next decade can be envisioned as the time when the first reproducibly efficacious combination regimes for cancer immunotherapy will become available and widely used in the clinic, as clinicians learn the best strategies and try to harness their potentially damaging effects.
authors.affiliation: Gene Therapy Division, Facultad de Medicina and Clinica Universitaria, Universidad de Navarra, Pamplona, Spain.
authors.forename: Iñigo
authors.initials: I
authors.lastname: Tirapu
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mazzolini
authors.forename: Mercedes
authors.initials: M
authors.lastname: Rodriguez-Calvillo
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Arina
authors.forename: Belen
authors.initials: B
authors.lastname: Palencia
authors.forename: Izaskun
authors.initials: I
authors.lastname: Gabari
authors.forename: Ignacio
authors.initials: I
authors.lastname: Melero
mesh_terms: D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D015551:Autoimmunity; D019013:CD40 Antigens / Q000378:metabolism; D060908:CTLA-4 Antigen; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates; D007167:Immunotherapy / Q000009:adverse effects; D009369:Neoplasms / Q000628:therapy*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D015375:Receptors, Interleukin-2; D000069594:Abatacept