title: Immunotherapy for gastric cancers: emerging role and future perspectives.
abstract: The broad use of immunotherapy is revolutionizing the treatment paradigms of many solid tumors. Although chemotherapy remains the treatment backbone for advanced gastric cancer, improvements in its molecular characterization and progresses in understanding its underpinning biology have supported clinical development of novel immunotherapies. However, the results of recent trials testing these new agents raise the question on how to identify the patients that could greatly benefit. Areas covered: This article summarizes the current understanding on the biology and the mechanisms underlying different clinical features of gastric cancers. Particularly, after a comprehensive literature search, we speculate whether specific molecular subsets of patients could derive more benefit from immunotherapy. Expert commentary: Most cancers may evade the immune response, which is normally regulated by a delicate balance between activating and inhibitory signals. For example, both CTLA-4 and PD-1, once linked to PD-L1/2, may inhibit T-cell signaling. The use of agent to harness the power of the immune system appears to be the ultimate frontier in gastric cancer treatment. While anti-CTLA-4 antibodies are minimally active, there is growing evidence for the efficacy of PD1/-L1 inhibitors. The search of predictive factors for immunotherapy will provide key hints towards the optimal use of these agents.
authors.affiliation: a Department Oncology , University Hospital of Udine , Udine , Italy.|b Department of Medical Area , University of Udine , Udine , Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Bonotto
authors.affiliation: a Department Oncology , University Hospital of Udine , Udine , Italy.|b Department of Medical Area , University of Udine , Udine , Italy.
authors.forename: Silvio Ken
authors.initials: SK
authors.lastname: Garattini
authors.affiliation: a Department Oncology , University Hospital of Udine , Udine , Italy.|b Department of Medical Area , University of Udine , Udine , Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Basile
authors.affiliation: a Department Oncology , University Hospital of Udine , Udine , Italy.|b Department of Medical Area , University of Udine , Udine , Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Ongaro
authors.affiliation: a Department Oncology , University Hospital of Udine , Udine , Italy.|b Department of Medical Area , University of Udine , Udine , Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Fanotto
authors.affiliation: a Department Oncology , University Hospital of Udine , Udine , Italy.|b Department of Medical Area , University of Udine , Udine , Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Cattaneo
authors.affiliation: a Department Oncology , University Hospital of Udine , Udine , Italy.|b Department of Medical Area , University of Udine , Udine , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cortiula
authors.affiliation: a Department Oncology , University Hospital of Udine , Udine , Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Iacono
authors.affiliation: a Department Oncology , University Hospital of Udine , Udine , Italy.
authors.forename: Giovanni Gerardo
authors.initials: GG
authors.lastname: Cardellino
authors.affiliation: a Department Oncology , University Hospital of Udine , Udine , Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Pella
authors.affiliation: a Department Oncology , University Hospital of Udine , Udine , Italy.
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Fasola
authors.affiliation: c Medical Oncology , University Hospital Careggi , Firenze , Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Antonuzzo
authors.affiliation: d Medical Oncology Unit , National Cancer Institute IRCCS "Giovanni Paolo II" , Bari , Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Silvestris
authors.affiliation: a Department Oncology , University Hospital of Udine , Udine , Italy.|e Department of Oncology , General Hospital San Bortolo, ULSS8 Berica , Vicenza , Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Aprile
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D060908:CTLA-4 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Gastric cancer; PD-L1; PD-L2; immunotherapy; molecular classification