Immune biomarkers in thymic epithelial tumors: expression patterns, prognostic value and comparison of diagnostic tests for PD-L1

Isabelle Rouquette, Estelle Taranchon-Clermont, Julia Gilhodes, Maria-Virginia Bluthgen, Romain Perallon, Lara Chalabreysse, Anne De Muret, Veronique Hofman, Alexander Marx, Marie Parrens, Veronique Secq, Vincent Thomas de Montpreville, Françoise Galateau-Salle, Pierre Brousset, Julie Milia, Nicolas Girard, Benjamin Besse, Thierry Jo Molina, Julien Mazières, Isabelle Rouquette, Estelle Taranchon-Clermont, Julia Gilhodes, Maria-Virginia Bluthgen, Romain Perallon, Lara Chalabreysse, Anne De Muret, Veronique Hofman, Alexander Marx, Marie Parrens, Veronique Secq, Vincent Thomas de Montpreville, Françoise Galateau-Salle, Pierre Brousset, Julie Milia, Nicolas Girard, Benjamin Besse, Thierry Jo Molina, Julien Mazières

Abstract

Background: Immunotherapy is currently under investigation in B3 Thymoma (TB3) and Thymic Carcinoma (TC). PD-L1 expression has been evaluated on a limited number of patients with selected antibodies. We aimed to analyze cohort of TB3 and TC with a panel of antibodies to assess the prevalence of PD-L1 expression, its prognostic value and to set up a reproducible test.

Methods: We retrospectively studied 103 patients samples of FFPE histologically confirmed TB3 (n = 53) and TC (n = 50) by expert pathologists within the RYTHMIC national network. We compared PD-L1, PD1, CD8 and PD-L2 expression and performed correlation with tumor types and patients outcomes. Four PD-L1 antibodies were tested, three of them validated as companion tests in lung cancer, one tested on two automates on whole section of tumors. We evaluated the percentage and intensity of both epithelial and immune stained cells.

Results: TB3 epithelial cells had a higher and more diffuse expression of PD-L1 than TC regardless the antibodies tested (p < 0.0001). Three out of four antibodies targeting PD-L1 tested on the DAKO autostainer gave similar staining. Concordance between antibodies was lower for PD-L1 staining on immune cells with no significant difference between TB3 and TC except on E1L3N antibody. PD-L2 antibody stained no tumor epithelial cells. High PD-L1 expression was correlated with a better overall survival for TB3 and was not correlated with tumor staging.

Conclusion: Frequent PD-L1 expression, particularly in TB3, paves the way for immunotherapy in TET (Thymic Epithelial Tumor). Otherwise, we have set up three reproducible LDT (laboratory-developed test) for four PD-L1 antibodies.

Keywords: B3 thymoma; Immunotherapy; PD-L1; Thymic carcinoma.

Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

© The Author(s). 2019.

Figures

Fig. 1
Fig. 1
PD-L1 Thymoma staining comparaison. Commercial Assays (CA): PDL1 22C3 PharmDx Dako (a); Ventana PD-L1 SP142 Assay (b), Ventana PD-L1 S263 Assay (c) Laboratory developed test (LDT): PD-L 1-E1L3N cell signaling technology (d); PDL1-SP142 Ventana (e)
Fig. 2
Fig. 2
Comparison of B3 Thymomas (TB3) (a to h) and Thymic Carcinoma (TC) (I to p) staining with Commercial Assays (CA) and Laboratory developed tests (LDT). HE staining (a, i); CA, PD-L1 22C3 PharmDx Dako (b, j); CA, Ventana PDL1 SP142 Assay (c, k); CA, Ventana PD-L1 S263 Assay (d, l); LDT PD-L1-E1L3N cell signaling technology (e, m); LDT PD-L1-SP142 Ventana (f, n); CA CD8-SP57 (g, o); CA PD1-NAT105 (h,p)
Fig. 3
Fig. 3
Overall survival according to histology
Fig. 4
Fig. 4
Relapse free survival according to histology
Fig. 5
Fig. 5
Relapse free survival according to antibody and 50% or 1% threshold

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