TY - JOUR
T1 - Toward a comprehensive view of cancer immune responsiveness
T2 - A synopsis from the SITC workshop
AU - Bedognetti, Davide
AU - Ceccarelli, Michele
AU - Galluzzi, Lorenzo
AU - Lu, Rongze
AU - Palucka, Karolina
AU - Samayoa, Josue
AU - Spranger, Stefani
AU - Warren, Sarah
AU - Wong, Kwok Kin
AU - Ziv, Elad
AU - Chowell, Diego
AU - Coussens, Lisa M.
AU - De Carvalho, Daniel D.
AU - Denardo, David G.
AU - Galon, Jérôme
AU - Kaufman, Howard L.
AU - Kirchhoff, Tomas
AU - Lotze, Michael T.
AU - Luke, Jason J.
AU - Minn, Andy J.
AU - Politi, Katerina
AU - Shultz, Leonard D.
AU - Simon, Richard
AU - Thórsson, Vésteinn
AU - Weidhaas, Joanne B.
AU - Ascierto, Maria Libera
AU - Ascierto, Paolo Antonio
AU - Barnes, James M.
AU - Barsan, Valentin
AU - Bommareddy, Praveen K.
AU - Bot, Adrian
AU - Church, Sarah E.
AU - Ciliberto, Gennaro
AU - De Maria, Andrea
AU - Draganov, Dobrin
AU - Ho, Winson S.
AU - McGee, Heather M.
AU - Monette, Anne
AU - Murphy, Joseph F.
AU - Nisticò, Paola
AU - Park, Wungki
AU - Patel, Maulik
AU - Quigley, Michael
AU - Radvanyi, Laszlo
AU - Raftopoulos, Harry
AU - Rudqvist, Nils Petter
AU - Snyder, Alexandra
AU - Sweis, Randy F.
AU - Valpione, Sara
AU - Butterfield, Lisa H.
AU - Disis, Mary L.
AU - Fox, Bernard A.
AU - Cesano, Alessandra
AU - Marincola, Francesco M.
N1 - Publisher Copyright:
© 2019 The Author(s).
PY - 2019/5/22
Y1 - 2019/5/22
N2 - 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.
AB - 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.
KW - Biomarker
KW - Cancer immune phenotype
KW - Cancer immune responsiveness (CIR)
KW - Germline molecular alterations
KW - Immune checkpoint inhibitor (ICI)
KW - Immune oncology (IO)
KW - Immunogenic cell death (ICD)
KW - Immunotherapy
KW - Somatic molecular alterations
KW - Tumor microenvironment (TME)
KW - Tumor mutational burden (TMB)
UR - http://www.scopus.com/inward/record.url?scp=85066470892&partnerID=8YFLogxK
U2 - 10.1186/s40425-019-0602-4
DO - 10.1186/s40425-019-0602-4
M3 - Review article
C2 - 31113486
AN - SCOPUS:85066470892
SN - 2051-1426
VL - 7
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
IS - 1
M1 - 131
ER -