TY - JOUR
T1 - Developing a definition of immune exclusion in cancer
T2 - Results of a modified Delphi workshop
AU - Clifton, Guy Travis
AU - Rothenberg, Mace
AU - Ascierto, Paolo Antonio
AU - Begley, Glenn
AU - Cecchini, Michael
AU - Eder, Joseph Paul
AU - Ghiringhelli, Francois
AU - Italiano, Antoine
AU - Kochetkova, Marina
AU - Li, Rong
AU - Mechta-Grigoriou, Fatima
AU - Pai, Sara I.
AU - Provenzano, Paolo
AU - Puré, Ellen
AU - Ribas, Antoni
AU - Schalper, Kurt A.
AU - Fridman, Wolf Herve
N1 - Publisher Copyright:
© 2023 BioMed Central Ltd.. All rights reserved.
PY - 2023/6/8
Y1 - 2023/6/8
N2 - Checkpoint inhibitors represent an effective treatment approach for a variety of cancers through their inhibition of immune regulatory pathways within the tumor microenvironment (TME). Unfortunately only a minority of patients with cancer achieve clinical benefit from immunotherapy, with the TME emerging as an important predictor of outcomes and sensitivity to therapy. The extent and pattern of T-cell infiltration can vary prominently within/across tumors and represents a biological continuum. Three immune profiles have been identified along this continuum: € immune-desert' or € T-cell cold' phenotype, € immune-active', € inflamed', or € T-cell hot' phenotype, and € immune excluded' phenotype. Of the three profiles, immune excluded remains the most ill-defined with no clear, universally accepted definition even though it is commonly associated with lack of response to immune checkpoint inhibitors and poor clinical outcomes. To address this, 16 multidisciplinary cancer experts from around the world were invited to participate in a symposium using a three-round modified Delphi approach. The first round was an open-ended questionnaire distributed via email and the second was an in-person discussion of the first round results that allowed for statements to be revised as necessary to achieve a maximum consensus (75% agreement) among the rating committee (RC). The final round questionnaire was distributed to the RC via email and had a 100% completion rate. The Delphi process resulted in moving us closer to a consensus definition for immune exclusion that is practical, clinically pertinent, and applicable across a wide range of cancer histologies. A general consensus of the role of immune exclusion in resistance to checkpoint therapy and five research priorities emerged from this process. Together, these tools could help efforts designed to address the underlying mechanisms of immune exclusion that span cancer types and, ultimately, aid in the development of treatments to target these mechanisms to improve patient outcomes.
AB - Checkpoint inhibitors represent an effective treatment approach for a variety of cancers through their inhibition of immune regulatory pathways within the tumor microenvironment (TME). Unfortunately only a minority of patients with cancer achieve clinical benefit from immunotherapy, with the TME emerging as an important predictor of outcomes and sensitivity to therapy. The extent and pattern of T-cell infiltration can vary prominently within/across tumors and represents a biological continuum. Three immune profiles have been identified along this continuum: € immune-desert' or € T-cell cold' phenotype, € immune-active', € inflamed', or € T-cell hot' phenotype, and € immune excluded' phenotype. Of the three profiles, immune excluded remains the most ill-defined with no clear, universally accepted definition even though it is commonly associated with lack of response to immune checkpoint inhibitors and poor clinical outcomes. To address this, 16 multidisciplinary cancer experts from around the world were invited to participate in a symposium using a three-round modified Delphi approach. The first round was an open-ended questionnaire distributed via email and the second was an in-person discussion of the first round results that allowed for statements to be revised as necessary to achieve a maximum consensus (75% agreement) among the rating committee (RC). The final round questionnaire was distributed to the RC via email and had a 100% completion rate. The Delphi process resulted in moving us closer to a consensus definition for immune exclusion that is practical, clinically pertinent, and applicable across a wide range of cancer histologies. A general consensus of the role of immune exclusion in resistance to checkpoint therapy and five research priorities emerged from this process. Together, these tools could help efforts designed to address the underlying mechanisms of immune exclusion that span cancer types and, ultimately, aid in the development of treatments to target these mechanisms to improve patient outcomes.
KW - tumor microenvironment
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U2 - 10.1136/jitc-2023-006773
DO - 10.1136/jitc-2023-006773
M3 - Article
C2 - 37290925
AN - SCOPUS:85162964955
SN - 2051-1426
VL - 11
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
IS - 6
M1 - e006773
ER -