title: Immunotherapy in gastrointestinal cancer: Recent results, current studies and future perspectives.
abstract: The new therapeutic approach of using immune checkpoint inhibitors as anticancer agents is a landmark innovation. Early studies suggest that immune checkpoint inhibition might also be effective in patients with gastrointestinal cancer. To improve the efficacy of immunotherapy, different strategies are currently under evaluation. This review summarises the discussion during the European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cancer Translational Research Meeting in Mainz in November 2014 and provides an update on the most recent results of immune therapy in gastrointestinal cancers. Knowledge of potential relationships between tumour cells and their microenvironment including the immune system will be essential in gastrointestinal malignancies. In this context, the density of T cell infiltration within colorectal cancer metastases has been associated with response to chemotherapy, and a high expression of programmed cell death ligand 1 (PD-L1) in advanced gastric cancer has been related with poor prognosis. Effective targets might include neo-antigens encoded from genes carrying tumour-specific somatic mutations. Tailored immunotherapy based on such mutations could enable the effective targeting of an individual patient's tumour with vaccines produced on demand. Other strategies considering checkpoint inhibitors have shown efficacy by targeting cytotoxic T-lymphocyte-associated protein 4 and PD-1 or PD-L1. DNA mismatch repair-deficient tumours appear to be potentially the best candidates for these therapies. Finally, the combination of oncolytic viruses with immunotherapy might boost antitumour activity as well. Further evaluation of these promising immunological therapeutic approaches will require large prospective clinical studies.
authors.affiliation: First Department of Internal Medicine, Johannes Gutenberg-University of Mainz, Mainz, Germany. Electronic address: markus.moehler@unimedizin-mainz.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Moehler
authors.affiliation: First Department of Internal Medicine, Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Delic
authors.affiliation: First Department of Internal Medicine, Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Goepfert
authors.affiliation: Institute of Pathology, Medizinische Fakultät Carl Gustav Carus, Technische Universität, Dresden, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Aust
authors.affiliation: Department of Pathology and GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands; Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
authors.forename: Heike I
authors.initials: HI
authors.lastname: Grabsch
authors.affiliation: Department of Medical Oncology, National Center of Tumor Diseases and University Medical Center Heidelberg, Heidelberg, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Halama
authors.affiliation: First Department of Internal Medicine, Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Heinrich
authors.affiliation: Department of Pathology, Ambroise Paré Hospital, Boulogne, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Julie
authors.affiliation: University Cancer Center Leipzig (UCCL), University Hospital Leipzig, Leipzig, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lordick
authors.affiliation: CaritasKlinikum St. Theresia, Saarbrücken, Germany.
authors.forename: Manfred P
authors.initials: MP
authors.lastname: Lutz
authors.affiliation: EORTC Statistics Department, Brussels, Belgium.
authors.forename: Murielle
authors.initials: M
authors.lastname: Mauer
authors.affiliation: Vall d'Hebron University Hospital and VHIO-Vall d'Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Alsina Maqueda
authors.affiliation: Institute of Immunology, University of Mainz, Mainz, Germany.
authors.forename: Hansjoerg
authors.initials: H
authors.lastname: Schild
authors.affiliation: Department of Internal Medicine, Marienhospital Darmstadt, Darmstadt, Germany.
authors.forename: Carl C
authors.initials: CC
authors.lastname: Schimanski
authors.affiliation: Multidisciplinary Oncology Center, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Anna-Dorothea
authors.initials: AD
authors.lastname: Wagner
authors.affiliation: Department of Medical Oncology, University of Geneva, Geneva, Switzerland.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Roth
authors.affiliation: Department of Medical Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D004812:Epidemiologic Methods; D005544:Forecasting; D005770:Gastrointestinal Neoplasms / Q000628:therapy*; D005819:Genetic Markers / Q000502:physiology; D006801:Humans; D007167:Immunotherapy / Q000379:methods / Q000639:trends*; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D050130:Oncolytic Virotherapy / Q000379:methods; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005819:Genetic Markers
keywords: Checkpoint inhibitors; Gastrointestinal cancer; Immunotherapy