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


Guy Travis Clifton, Parthenon Therapeutics, Boston, Massachusetts, USA
Mace Rothenberg, Consultant, Parthenon Therapeutics, Boston, Massachusetts, USA.
Paolo Antonio Ascierto, Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, IRCCS Fondazione "G. Pascale", Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Campania, Italy.
Glenn Begley, Parthenon Therapeutics, Boston, Massachusetts, USA.
Michael Cecchini, Department of Internal Medicine, Division of Medical Oncology, Yale School of Medicine, New Haven, Connecticut, USA.
Joseph Paul Eder, Parthenon Therapeutics, Boston, Massachusetts, USA.
Francois Ghiringhelli, Department of Medical Oncology, Georges François Leclerc Cancer Center-UNICANCER, Dijon, France.
Antoine Italiano, Early Phase Trial Unit, Institut Bergonié, Bordeaux 33000, France.
Marina Kochetkova, Centre for Cancer Biology, University of South Australia, Adelaide, South Australia, Australia.
Rong Li, Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Fatima Mechta-Grigoriou, Stress and Cancer Laboratory, Institut Curie, INSERM, Paris, France.
Sara I. Pai, Department of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Paolo Provenzano, Department of Biomedical Engineering, University of Minnesota System, Minneapolis, Minnesota, USA.
Ellen Puré, Department of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.
Antoni Ribas, Division of Hematology and Oncology, UCLA David Geffen School of Medicine, Los Angeles, California, USA.
Kurt A. Schalper, Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
Wolf Herve Fridman, Department of Immunology, Inflammation and Cancer, Centre de Recherche des Cordeliers, Paris, France.

Document Type

Journal Article

Publication Date



Journal for immunotherapy of cancer








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.


Biochemistry and Molecular Medicine