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      Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge”, Napoli, December 5 th 2015

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Harnessing the immune system and preventing immune escape, the immunotherapy of cancer provides great potential for clinical application, in broad patient populations, achieving both conventional and unconventional clinical responses. After the substantial advances in melanoma, the focus of cancer immunotherapy has expanded to include many other cancers. Targeting immune checkpoints and further mechanisms used by tumors to avoid anticancer immunity, different approaches are under evaluation, including combination therapies.

          The first Immunotherapy Bridge meeting focused on various cancer types including melanoma, non-small cell lung cancer, renal cell, breast and ovarian carcinoma, and discussed mechanisms of action of single agents and combination strategies, and the prediction of clinical responses.

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          Most cited references42

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          Combining radiotherapy and cancer immunotherapy: a paradigm shift.

          Silvia Formenti, Sandra Demaria (2013)
          The therapeutic application of ionizing radiation has been largely based on its cytocidal power combined with the ability to selectively target tumors. Radiotherapy effects on survival of cancer patients are generally interpreted as the consequence of improved local control of the tumor, directly decreasing systemic spread. Experimental data from multiple cancer models have provided sufficient evidence to propose a paradigm shift, whereby some of the effects of ionizing radiation are recognized as contributing to systemic antitumor immunity. Recent examples of objective responses achieved by adding radiotherapy to immunotherapy in metastatic cancer patients support this view. Therefore, the traditional palliative role of radiotherapy in metastatic disease is evolving into that of a powerful adjuvant for immunotherapy. This combination strategy adds to the current anticancer arsenal and offers opportunities to harness the immune system to extend survival, even among metastatic and heavily pretreated cancer patients. We briefly summarize key evidence supporting the role of radiotherapy as an immune adjuvant. A critical appraisal of the current status of knowledge must include potential immunosuppressive effects of radiation that can hamper its capacity to convert the irradiated tumor into an in situ, individualized vaccine. Moreover, we discuss some of the current challenges to translate this knowledge to the clinic as more trials testing radiation with different immunotherapies are proposed.
          Article 0 comments Cited 373 times – based on 0 reviews     Review now
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            Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer.

            Sandra Demaria, Noriko Kawashima, Anne Marie Yang … (2005)
            Ionizing radiation therapy (RT) is an important component in the management of breast cancer. Although the primary tumor can be successfully treated by surgery and RT, metastatic breast cancer remains a therapeutic challenge. Here we tested the hypothesis that the combination of RT to the primary tumor with CTLA-4 blockade can elicit antitumor immunity inhibiting the metastases. The poorly immunogenic metastatic mouse mammary carcinoma 4T1 was used as a model. Mice were injected s.c. with 4T1 cells, and treatment was started 13 days later when the primary tumors measured 5 mm in average diameter. Mice were randomly assigned to four treatment groups receiving: (1) control IgG (IgG), (2) RT + IgG, (3) 9H10 monoclonal antibody against CTLA-4, (4) RT + 9H10. RT was delivered to the primary tumor by one or two fractions of 12 Gy. 9H10 and IgG were given i.p. thrice after RT. Consistent with the fact that 4T1 is poorly immunogenic, 9H10 alone did not have any effect on primary tumor growth or survival. RT was able to delay the growth of the primary irradiated tumor, but in the absence of 9H10 survival was similar to that of control mice. In contrast, mice treated with RT + 9H10 had a statistically significant survival advantage. The increased survival correlated with inhibition of lung metastases formation and required CD8+ but not CD4+ T cells. The combination of local RT with CTLA-4 blockade is a promising new immunotherapeutic strategy against poorly immunogenic metastatic cancers.
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              Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial.

              Encouse B Golden, Arpit Chhabra, Abraham Chachoua … (2015)
              An abscopal response describes radiotherapy-induced immune-mediated tumour regression at sites distant to the irradiated field. Granulocyte-macrophage colony-stimulating factor is a potent stimulator of dendritic cell maturation. We postulated that the exploitation of the pro-immunogenic effects of radiotherapy with granulocyte-macrophage colony-stimulating factor might result in abscopal responses among patients with metastatic cancer.
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                Author and article information

                Contributors
                Paolo A. Ascierto:
                ORCID: http://orcid.org/0000-0002-8322-475X
                +39 081 5903236 , +39 081 5903841 , paolo.ascierto@gmail.com
                Maria Libera Ascierto: asciertoml@jhu.edu
                Silvia Formenti: formenti@med.cornell.edu
                Sacha Gnjatic: sacha.gnjatic@mssm.edu
                Hans Hammers: hans.hammers@utsouthwestern.edu
                Vera Hirsh: vera.hirsh@muhc.mcgill.ca
                Rolf Kiessling: rolf.kiessling@ki.se
                Ignacio Melero: imelero@unav.es
                Rita Nanda: rnanda@medicine.bsd.uchicago.edu
                Graham Pawelec: graham.pawelec@uni-tuebingen.de
                Sandro Pignata: s.pignata@istitutotumori.na.it
                Pedro Romero: pedro.romero@unil.ch
                Daniel E. Speiser: daniel.speiser@unil.ch
                Bernard A. Fox: foxb@foxlab.org
                Francesco M. Marincola: fmarincola@sidra.org
                Journal
                Journal ID (nlm-ta): J Immunother Cancer
                Journal ID (iso-abbrev): J Immunother Cancer
                Title: Journal for Immunotherapy of Cancer
                Publisher: BioMed Central (London )
                ISSN (Electronic): 2051-1426
                Publication date (Electronic): 18 October 2016
                Publication date PMC-release: 18 October 2016
                Publication date Collection: 2016
                Volume: 4
                Electronic Location Identifier: 62
                Affiliations
                [1 ]Istituto Nazionale Tumori “Fondazione G. Pascale”, Naples, Italy
                [2 ]Melanoma. Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione “G. Pascale” Via Mariano Semmola, 80131 Napoli, Italy
                [3 ]Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD USA
                [4 ]Department of Radiation Oncology, Weill Cornell Medical College, New York, NY USA
                [5 ]Tisch Cancer Institute, Hematology/Oncology, Immunology, Icahn School of Medicine at Mount Sinai, New York, USA
                [6 ]UT Southwestern, Kidney Cancer Program, Dallas, TX USA
                [7 ]McGill University, Royal Victoria Hospital, Montreal, Canada
                [8 ]Department of Oncology/Pathology, Karolinska Institutet, Stockholm, Sweden
                [9 ]Centro de Investigación Médica Aplicada, and Clinica Universidad de Navarra, Pamplona, Navarra Spain
                [10 ]Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL USA
                [11 ]Second Department of Internal Medicine, University of Tuebingen, Tuebingen, Germany
                [12 ]Department of Oncology and Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland
                [13 ]Oregon Health and Science University, Providence Cancer Center, Portland Medical Center, Portland, OR USA
                [14 ]Sidra Medical and Research Centre, Doha, Qatar
                Author information
                http://orcid.org/0000-0002-8322-475X
                Article
                Publisher ID: 168
                DOI: 10.1186/s40425-016-0168-3
                PMC ID: 5067891
                SO-VID: 4962e4d9-56f7-4ee2-8147-79c649d48e95
                Copyright © © The Author(s). 2016
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 11 August 2016
                Date accepted : 15 September 2016
                Categories
                Subject: Meeting Report
                Custom metadata
                issue-copyright-statement © The Author(s) 2016

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