PDL1 expression in inflammatory breast cancer is frequent and predicts for the pathological response to chemotherapy

// François Bertucci 1, 2, 3 , Pascal Finetti 1 , Cécile Colpaert 4 , Emilie Mamessier 1 , Maxime Parizel 4 , Luc Dirix 5 , Patrice Viens 1, 2, 3 , Daniel Birnbaum 1 , Steven van Laere 5 1 Département d’Oncologie Moléculaire, “Equipe Labellisée Ligue Contre le Cancer”, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Marseille, France 2 Département d’Oncologie Médicale, CRCM, Institut Paoli-Calmettes, Marseille, France 3 Faculté de Médecine, Aix-Marseille Université, Marseille, France 4 Department of Pathology, GZA Hospitals Sint-Augustinus, Antwerp, Belgium 5 Center for Oncological Research (CORE), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp Belgium Correspondence to: François Bertucci, e-mail: bertuccif@ipc.unicancer.fr Keywords: chemotherapy, inflammatory breast cancer, immune response, PDL1, survival Received: January 23, 2015 Accepted: March 23, 2015 Published: April 11, 2015 ABSTRACT We retrospectively analyzed PDL1 mRNA expression in 306 breast cancer samples, including 112 samples of an aggressive form, inflammatory breast cancer (IBC). PDL1 expression was heterogeneous, but was higher in IBC than in non-IBC. Compared to normal breast samples, PDL1 was overexpressed in 38% of IBC. In IBC, PDL1 overexpression was associated with estrogen receptor-negative status, basal and ERBB2-enriched aggressive subtypes, and clinico-biological signs of anti-tumor T-cell cytotoxic response. PDL1 overexpression was associated with better pathological response to chemotherapy, independently of histo-clinical variables and predictive gene expression signatures. No correlation was found with metastasis-free and overall specific survivals. In conclusion, PDL1 overexpression in IBC correlated with better response to chemotherapy. This seemingly counterintuitive correlation between expression of an immunosuppressive molecule and improved therapeutic response may be resolved if PDL1 expression is viewed as a surrogate marker of a strong antitumor immune response among patients treated with immunogenic chemotherapy. In such patients, PDL1 inhibition could protect activated T-cells or reactivate inhibited T-cells and improve the therapeutic response, notably when associated with immunogenic chemotherapy.