Brain metastasis PD-L1 and CD8 expression is dependent on primary tumor type and its PD-L1 and CD8 status
Authors: Michel Peoc&#x27;h
Jean Marc Dumollard
Tiphanie Picot
Jean Luc Perrot
Nicolas Magne
Francois Vassal
Mousa Mobarki
Georgia Karpathiou
Marios Froudarakis
Fabien Forest
Sirine Hathroubi
Florian Camy
Francois Casteillo
Journal: Journal for ImmunoTherapy of Cancer (2020)
Discipline: IMMUNOLOGY
Keywords: CD8-positive T-lymphocytes; biomarkers, tumor; brain neoplasms; immunotherapy; programmed cell death 1 receptor.
Affiliations: Pathology, University Hospital of Saint-Etienne, Saint-Etienne, France., Pathology, University Hospital of Saint-Etienne, Saint-Etienne, France ., Radiotherapy, Lucien Neuwirth Cancer Institute, Saint-Etienne, France., Dermatology, University Hospital of Saint-Etienne, Saint-Etienne, France., Neurosurgery, University Hospital of Saint-Eteinne, Saint-Etienne, France., Faculty of Medicine, Jazan University, Jazan, Saudi Arabia., Pneumology and Thoracic Oncology, University Hospital of Saint-Etienne, Saint-Etienne, France.

Abstract:  Background: Brain metastases (Bmets) are frequent; however, limited data exist on the efficacy of immunotherapy in these lesions. The aims of the study were to analyze the immunohistochemical expressions of programmed death ligand 1 (PD-L1) and CD8 in Bmets and to compare them with their expressions in paired primary tumors, as well as correlate the results with clinicopathological features. Methods: This is a retrospective study of 233 patients with Bmets and 111 paired primaries. Clinical, histological, and molecular data were recorded and compared with the immunohistochemical results of PD-L1 and CD8 expressions. The statistical analysis included χ2 test, Cramer's V test, factorial analyses of variance, simple regression analysis, and Kaplan-Meier analysis with log-rank product limit estimation. Results: PD-L1 expression was found in 23.6% of Bmets and in 29.0% of primary tumors with concordant expression between them in 75.5% of cases. Bmets PD-L1 expression was associated with primary tumor PD-L1 expression and the primary tumor type. Significant CD8 peritumoral expression was found in 68.6% of Bmets and in 87.7% of primary tumors. CD8 expression was concordant between primary and metastatic tumors in 73.3% of cases. Bmets CD8 expression was associated with primary tumor CD8 expression and primary tumor type. PD-L1 expression was associated with CD8 expression in both primary and metastatic tumors. The concordance between primary and metastatic tumor PD-L1 expression was independent of all factors studied. The concordance between primary and metastatic CD8 expressions was marginally associated to the time of Bmets development. No prognostic role for PD-L1 and CD8 expression in Bmets was found. Conclusion: PD-L1 and CD8 Bmets expressions are associated with the primary tumor type and its PD-L1 and CD8 expressions. No factor predicts the discordance for PD-L1 expression, while time to Bmets development is associated with CD8 expression discordance. 

Retracted: No

PubPeer comments:
 The statistical analysis of this work needs to be completely revised. The number of correlations is large, with no calculation of the risk of false discovery. The survival analysis is wrong with different cancers all included in the same analysis. There is no multivariate analysis, which greatly diminishes the significance of this work, if not completely negates it. ,