Immune-enrichment of non-small cell lung cancer baseline biopsies for multiplex profiling define prognostic immune checkpoint combinations for patient stratification View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Anne Monette, Derek Bergeron, Amira Ben Amor, Liliane Meunier, Christine Caron, Anne-Marie Mes-Masson, Nidhameddine Kchir, Kamel Hamzaoui, Igor Jurisica, Réjean Lapointe

ABSTRACT

BACKGROUND: Permanence of front-line management of lung cancer by immunotherapies requires predictive companion diagnostics identifying immune-checkpoints at baseline, challenged by the size and heterogeneity of biopsy specimens. METHODS: An innovative, tumor heterogeneity reducing, immune-enriched tissue microarray was constructed from baseline biopsies, and multiplex immunofluorescence was used to profile 25 immune-checkpoints and immune-antigens. RESULTS: Multiple immune-checkpoints were ranked, correlated with antigen presenting and cytotoxic effector lymphocyte activity, and were reduced with advancing disease. Immune-checkpoint combinations on TILs were associated with a marked survival advantage. Conserved combinations validated on more than 11,000 lung, breast, gastric and ovarian cancer patients demonstrate the feasibility of pan-cancer companion diagnostics. CONCLUSIONS: In this hypothesis-generating study, deepening our understanding of immune-checkpoint biology, comprehensive protein-protein interaction and pathway mapping revealed that redundant immune-checkpoint interactors associate with positive outcomes, providing new avenues for the deciphering of molecular mechanisms behind effects of immunotherapeutic agents targeting immune-checkpoints analyzed. More... »

PAGES

86

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s40425-019-0544-x

    DOI

    http://dx.doi.org/10.1186/s40425-019-0544-x

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1113050645

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30922393


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