AI Article Synopsis

  • Checkpoint inhibitors are a cancer treatment that works by blocking immune regulatory pathways, but only a small number of patients benefit from this therapy, with the tumor microenvironment (TME) playing a key role in treatment outcomes.
  • *Three T-cell infiltration profiles were identified: 'immune-desert' (T-cell cold), 'immune-active' (T-cell hot), and 'immune excluded,' the latter being poorly defined and linked to negative responses to treatment.
  • *A global symposium involving 16 cancer experts used a modified Delphi approach to reach a consensus on the definition of immune exclusion and its role in resistance to checkpoint therapy, identifying five research priorities to improve treatment development.*

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10254706PMC
http://dx.doi.org/10.1136/jitc-2023-006773DOI Listing

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