Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop

Journal for ImmunoTherapy of Cancer

Harry Raftopoulos¹  Anne Monette²  Joanne B. Weidhaas³  Lisa M. Coussens⁴  Heather M. McGee⁵  Paolo Antonio Ascierto⁶  Andrea De Maria⁷  Daniel D. De Carvalho⁸  Wungki Park⁹  Diego Chowell⁹  Winson S. Ho^1,10  Alexandra Snyder^1,11  Elad Ziv^1,12  Stefani Spranger^1,13  David G. DeNardo^1,14  Leonard D. Shultz^1,15  Karolina Palucka^1,16  Vésteinn Thórsson^1,17  Bernard A. Fox^1,18  Michele Ceccarelli^1,19  Josue Samayoa^1,19  Maulik Patel^1,19  James M. Barnes^1,19  Rongze Lu^1,19  Laszlo Radvanyi^2,20  Gennaro Ciliberto^2,21  Paola Nisticò^2,21  Jason J. Luke^2,22  Randy F. Sweis^2,22  Tomas Kirchhoff^2,23  Praveen K. Bommareddy^2,24  Andy J. Minn^2,25  Michael T. Lotze^2,26  Sara Valpione^2,27  Mary L. Disis^2,28  Katerina Politi^2,29  Nils-Petter Rudqvist^3,30  Lorenzo Galluzzi^3,31  Valentin Barsan^3,32  Dobrin Draganov^3,33  Joseph F. Murphy^3,34  Jérôme Galon^3,35  Adrian Bot^3,36  Howard L. Kaufman^3,37  Sarah E. Church^3,38  Sarah Warren^3,38  Alessandra Cesano^3,38  Kwok-Kin Wong^3,39  Richard Simon^4,40  Francesco M. Marincola^4,41  Davide Bedognetti^4,42  Maria Libera Ascierto^4,43  Michael Quigley^4,44  Lisa H. Butterfield^4,45 

[1] 0000 0000 8613 9871, grid.419670.d, Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ, USA;0000 0000 9401 2774, grid.414980.0, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada;0000 0000 9632 6718, grid.19006.3e, University of California, Los Angeles, Los Angeles, CA, USA;0000 0000 9758 5690, grid.5288.7, Oregon Health & Science University, Portland, OR, USA;0000 0001 0670 2351, grid.59734.3c, Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA;0000 0001 0807 2568, grid.417893.0, Istituto Nazionale Tumori-IRCCS Fondazione ‘G. Pascale’, Naples, Italy;0000 0001 2151 3065, grid.5606.5, Università degli Studi di Genova and Ospedale Policlinico San Martino IRCCS, Genoa, Italy;0000 0001 2157 2938, grid.17063.33, Department of Medical Biophysics, Princess Margaret Cancer Centre University Health Network, University of Toronto, Toronto, Canada;0000 0001 2171 9952, grid.51462.34, Memorial Sloan Kettering Cancer Center, New York, NY, USA;0000 0001 2193 0096, grid.223827.e, Department of Neurosurgery, Division of Pediatric Neurosurgery, Primary Children’s Hospital, University of Utah, Salt Lake City, UT, USA;0000 0001 2260 0793, grid.417993.1, Merck & Co., Kenilworth, NJ, USA;0000 0001 2297 6811, grid.266102.1, University of California, San Francisco, San Francisco, CA, USA;0000 0001 2341 2786, grid.116068.8, Koch Institute for Integrative Cancer Research at MIT, Cambridge, MT, USA;0000 0001 2355 7002, grid.4367.6, Washington University School of Medicine in St. Louis, St. Louis, MO, USA;0000 0004 0374 0039, grid.249880.f, The Jackson Laboratory Cancer Center, Bar Harbor, ME, USA;0000 0004 0374 0039, grid.249880.f, The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA;0000 0004 0463 2320, grid.64212.33, Institute for Systems Biology, Seattle, WA, USA;0000 0004 0463 5556, grid.415286.c, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Cancer Institute, Portland, OR, USA;0000 0004 0572 4227, grid.431072.3, AbbVie, Redwood City, CA, USA;0000 0004 0626 690X, grid.419890.d, Ontario Institute for Cancer Research, Toronto, Ontario, Canada;0000 0004 1760 5276, grid.417520.5, IRCCS Istituto Nazionale Tumori Regina Elena, Rome, Italy;0000 0004 1936 7822, grid.170205.1, University of Chicago, Chicago, IL, USA;0000 0004 1936 8753, grid.137628.9, Perlmutter Comprehensive Cancer Center, New York University School of Medicine, New York University Langone Health New York, New York, NY, USA;0000 0004 1936 8796, grid.430387.b, Rutgers University, New Brunswick, NJ, USA;0000 0004 1936 8972, grid.25879.31, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA;0000 0004 1936 9000, grid.21925.3d, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA;0000000121662407, grid.5379.8, CRUK Manchester Institute and The Christie NHS Foundation Trust, The University of Manchester, Manchester, UK;0000000122986657, grid.34477.33, University of Washington, Seattle, WA, USA;0000000419368710, grid.47100.32, Yale School of Medicine, New Haven, CT, USA;000000041936877X, grid.5386.8, Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA;000000041936877X, grid.5386.8, Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA;Sandra and Edward Meyer Cancer Center, New York, NY, USA;0000 0001 2188 0914, grid.10992.33, Université Paris Descartes/Paris V, Paris, France;0000000419368956, grid.168010.e, Stanford University, Stanford, CA, USA;Calidi Biotherapeutics, San Diego, CA, USA;Caprion Biosciences Inc., Montreal, QC, Canada;INSERM, Laboratory of Integrative Cancer Immunology, Equipe Labellisée Ligue Contre le Cancer, Sorbonne Université, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot; Centre de Recherche des Cordeliers, F-75006, Paris, France;Kite, a Gilead Company, Santa Monica, CA, USA;Massachusetts General Hospital, Boston, MA, USA and Replimune, Inc., Woburn, MA, USA;NanoString Technologies, Inc., Seattle, WA, USA;Perlmutter Cancer Center, New York Langone Health, New York, NY, USA;R. Simon Consulting, Potomac, MD, USA;Refuge Biotechnologies Inc., 1505 Adams Drive, Suite D, 94025, Menlo Park, CA, USA;Sidra Medicine, Doha, Qatar;grid.418152.b, MedImmune, Gaithersberg, MD, USA;grid.419971.3, Bristol-Myers Squibb Company, Redwood City, CA, USA;grid.489192.f, Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA;

关键词: Cancer immune responsiveness (CIR);    Immune checkpoint inhibitor (ICI);    Immune oncology (IO);    Immunotherapy;    Tumor microenvironment (TME);    Tumor mutational burden (TMB);    Immunogenic cell death (ICD);    Biomarker;    Germline molecular alterations;    Somatic molecular alterations;    Cancer immune phenotype;   

DOI  :  10.1186/s40425-019-0602-4

来源: publisher

【 摘 要 】

Tumor immunology has changed the landscape of cancer treatment. Yet, not all patients benefit as cancer immune responsiveness (CIR) remains a limitation in a considerable proportion of cases. The multifactorial determinants of CIR include the genetic makeup of the patient, the genomic instability central to cancer development, the evolutionary emergence of cancer phenotypes under the influence of immune editing, and external modifiers such as demographics, environment, treatment potency, co-morbidities and cancer-independent alterations including immune homeostasis and polymorphisms in the major and minor histocompatibility molecules, cytokines, and chemokines. Based on the premise that cancer is fundamentally a disorder of the genes arising within a cell biologic process, whose deviations from normality determine the rules of engagement with the host’s response, the Society for Immunotherapy of Cancer (SITC) convened a task force of experts from various disciplines including, immunology, oncology, biophysics, structural biology, molecular and cellular biology, genetics, and bioinformatics to address the complexity of CIR from a holistic view. The task force was launched by a workshop held in San Francisco on May 14–15, 2018 aimed at two preeminent goals: 1) to identify the fundamental questions related to CIR and 2) to create an interactive community of experts that could guide scientific and research priorities by forming a logical progression supported by multiple perspectives to uncover mechanisms of CIR. This workshop was a first step toward a second meeting where the focus would be to address the actionability of some of the questions identified by working groups. In this event, five working groups aimed at defining a path to test hypotheses according to their relevance to human cancer and identifying experimental models closest to human biology, which include: 1) Germline-Genetic, 2) Somatic-Genetic and 3) Genomic-Transcriptional contributions to CIR, 4) Determinant(s) of Immunogenic Cell Death that modulate CIR, and 5) Experimental Models that best represent CIR and its conversion to an immune responsive state. This manuscript summarizes the contributions from each group and should be considered as a first milestone in the path toward a more contemporary understanding of CIR. We appreciate that this effort is far from comprehensive and that other relevant aspects related to CIR such as the microbiome, the individual’s recombined T cell and B cell receptors, and the metabolic status of cancer and immune cells were not fully included. These and other important factors will be included in future activities of the taskforce. The taskforce will focus on prioritization and specific actionable approach to answer the identified questions and implementing the collaborations in the follow-up workshop, which will be held in Houston on September 4–5, 2019.

【 授权许可】

CC BY