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J Immunother Cancer. 2019 May 22;7(1):131. doi: 10.1186/s40425-019-0602-4.

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

Author information

1
Sidra Medicine, Doha, Qatar.
2
AbbVie, Redwood City, CA, USA.
3
Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
4
Sandra and Edward Meyer Cancer Center, New York, NY, USA.
5
Université Paris Descartes/Paris V, Paris, France.
6
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
7
Koch Institute for Integrative Cancer Research at MIT, Cambridge, MT, USA.
8
NanoString Technologies, Inc., Seattle, WA, USA.
9
Perlmutter Cancer Center, New York Langone Health, New York, NY, USA.
10
University of California, San Francisco, San Francisco, CA, USA.
11
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
12
Oregon Health & Science University, Portland, OR, USA.
13
Department of Medical Biophysics, Princess Margaret Cancer Centre University Health Network, University of Toronto, Toronto, Canada.
14
Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
15
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.
16
Massachusetts General Hospital, Boston, MA, USA and Replimune, Inc., Woburn, MA, USA.
17
Perlmutter Comprehensive Cancer Center, New York University School of Medicine, New York University Langone Health New York, New York, NY, USA.
18
UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
19
University of Chicago, Chicago, IL, USA.
20
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA.
21
Yale School of Medicine, New Haven, CT, USA.
22
The Jackson Laboratory Cancer Center, Bar Harbor, ME, USA.
23
R. Simon Consulting, Potomac, MD, USA.
24
Institute for Systems Biology, Seattle, WA, USA.
25
University of California, Los Angeles, Los Angeles, CA, USA.
26
MedImmune, Gaithersberg, MD, USA.
27
Istituto Nazionale Tumori-IRCCS Fondazione 'G. Pascale', Naples, Italy.
28
Stanford University, Stanford, CA, USA.
29
Rutgers University, New Brunswick, NJ, USA.
30
Kite, a Gilead Company, Santa Monica, CA, USA.
31
IRCCS Istituto Nazionale Tumori Regina Elena, Rome, Italy.
32
Università degli Studi di Genova and Ospedale Policlinico San Martino IRCCS, Genoa, Italy.
33
Calidi Biotherapeutics, San Diego, CA, USA.
34
Department of Neurosurgery, Division of Pediatric Neurosurgery, Primary Children's Hospital, University of Utah, Salt Lake City, UT, USA.
35
Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
36
Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.
37
Caprion Biosciences Inc., Montreal, QC, Canada.
38
Bristol-Myers Squibb Company, Redwood City, CA, USA.
39
Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
40
Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ, USA.
41
Merck & Co., Kenilworth, NJ, USA.
42
CRUK Manchester Institute and The Christie NHS Foundation Trust, The University of Manchester, Manchester, UK.
43
Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
44
Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
45
Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
46
University of Washington, Seattle, WA, USA.
47
Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Cancer Institute, Portland, OR, USA.
48
Refuge Biotechnologies Inc., 1505 Adams Drive, Suite D, Menlo Park, CA, 94025, USA. franco.marincola@refugebiotech.com.

Abstract

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.

KEYWORDS:

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

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