Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5715756 | Annales de Pathologie | 2017 | 18 Pages |
Abstract
Tumoral immune environment is a major component of cancer. Its composition and its organization represent a reproducible characteristic of tumors and a validated prognostic factor. In non-small cell lung cancer (NSCLC), cytotoxic T CD8+ lymphocyte density, associated with a Th1Â environment and tertiary lymphoid structures impacts survival. Tumor cell-immune cell interaction is targeted by PD1/PD-L1Â inhibitors. In advanced NSCLC, PD1/PD-L1Â inhibitors are more effective than second-line chemotherapy. Pembrolizumab outperforms first-line chemotherapy in NSCLC strongly positive for PD-L1. PD1/PD-L1Â inhibitors are currently tested in mesothelioma and thymic tumors. PD-L1Â expression evaluated with immunochemistry is the most studied predictive biomarker of PD1/PD-L1Â inhibitor efficacy. Tumor and immune cell expression of PD-L1Â is still difficult to evaluate because of intra-tumoral heterogeneity and expression modulation by the microenvironment. Four commercial diagnostic antibodies are in development, with differences concerning recognized epitopes, methodology of evaluation of PD-L1Â expression, positivity threshold, kit and platforms used. Clinical trials in NSCLC have shown that patients with tumors strongly positive for PD-L1Â derived the best clinical benefit with PD1/PD-L1Â inhibitors whereas clinical benefit is less common in tumors negative for PD-L1. PD-L1Â expression is not a perfect biomarker since some PD-L1Â negative NSCLC respond to PD1/PD-L1Â inhibitors and some PD-L1Â positive NSCLC do not. PD-L1Â testing is likely to be implemented in daily practice for selection of advanced NSCLC that will be treated with pembrolizumab, underscoring the relevance of ongoing harmonization studies of the use of the different antibodies available for PD-L1Â testing.
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Authors
Michaël Duruisseaux, Isabelle Rouquette, Julien Adam, Alexis Cortot, Aurélie Cazes, Laure Gibault, Diane Damotte, Sylvie Lantuejoul,