Immune biomarkers PD-1/PD-L1 and TLR3 in malignant pleural mesotheliomas

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• 作者：Christelle Combaz-Lair ; MD^a ; Franç ; oise Galateau-Sallé ; MD ; PhD^b ; Anne McLeer-Florin ; PhD^c ; Nolwenn Le Stang^d ; Laurence David-Boudet^a ; Mickael Duruisseaux ; MD ; PhD^e ; Gilbert R. Ferretti ; MD ; PhD^f ; Elisabeth Brambilla ; MD ; PhD^a ; Serge Lebecque ; MD ; PhD^g ; Sylvie Lantuejoul ; MD ; PhD^h ; ^{sylvie.lantuejoul@lyon.unicancer.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Pleura ; Mesothelioma ; Immunohistochemistry ; PD-L1 ; PD-1 ; TLR3 ; TILs
• 刊名：Human Pathology
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：52
• 期：Complete
• 页码：9-18
• 全文大小：1349 K

文摘

Malignant pleural mesothelioma (MPM) is an aggressive tumor with no effective therapy. However PD-L1/PD-1 immunity checkpoint therapies gave encouraging results; TLR3 is a programmed death factor, which triggering up-regulates PD-L1. As PD-1/PD-L1 blocking antibodies could restore antitumor immune responses alone or in combination with TLR3 agonists, we investigated PD-L1/PD-1 and TLR3 expressions in MPM to select patients for immunotherapy. Sixty-eight pleural surgical specimens, including 58 MPM (epithelioid, n = 34; biphasic, n = 11; sarcomatoid, n = 13) and 10 benign lesions, were studied. PD-L1 expression was assessed using E1L3N and SP142 clones in tumor cells (TCs) and in tumor-infiltrating lymphocytes (TILs) (positivity threshold of 1%), and compared with overall survival. PD-1, CD3 and CD8 expression by TILs, and TLR3 expression by TCs were analyzed concomitantly. PD-L1 was more expressed by sarcomatoid subtype than by other MPM (62% versus 23% and 9% for E1L3N; 38% versus 11% for SP142) (P = .01 and .04, respectively). Specificity and sensitivity of E1L3N and SP142 were of 53% and 98%, and 90% and 86%, respectively. PD-L1 expression by TILs and TCs correlated for SP142 (P = .023), and PD-L1 SP142 expression by TCs was associated with shorter overall survival (P = .016). TLR3 was expressed in most MPM, but weakly in sarcomatoid MPM. We confirm by comparing two commercially available antibodies that PD-L1 expression is higher in sarcomatoid MPM and correlates with a shorter survival. Whereas TLR3 agonists could be tested in MPM expressing TLR3, the sarcomatoid subtype could benefit from anti–PD-L1/PD-1 therapies alone or in combination.