[HTML][HTML] Immune-enrichment of non-small cell lung cancer baseline biopsies for multiplex profiling define prognostic immune checkpoint combinations for patient …

A Monette, D Bergeron, A Ben Amor, L Meunier… - … for ImmunoTherapy of …, 2019 - Springer
A Monette, D Bergeron, A Ben Amor, L Meunier, C Caron, AM Mes-Masson, N Kchir…
Journal for ImmunoTherapy of Cancer, 2019Springer
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 …
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.
Springer