Developing a definition of immune exclusion in cancer: Results of a modified Delphi workshop

Guy Travis Clifton, Mace Rothenberg, Paolo Antonio Ascierto, Glenn Begley, Michael Cecchini, Joseph Paul Eder, Francois Ghiringhelli, Antoine Italiano, Marina Kochetkova, Rong Li, Fatima Mechta-Grigoriou, Sara I. Pai, Paolo Provenzano, Ellen Puré, Antoni Ribas, Kurt A. Schalper, Wolf Herve Fridman

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere006773
JournalJournal for ImmunoTherapy of Cancer
Volume11
Issue number6
DOIs
StatePublished - Jun 8 2023

Bibliographical note

Publisher Copyright:
© 2023 BioMed Central Ltd.. All rights reserved.

Keywords

  • tumor microenvironment

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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