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Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression

Authors: Vanhersecke, Lucile; Brunet, Maxime; Guégan, Jean-Philippe; Rey, Christophe; Bougouin, Antoine; Cousin, Sophie; Le Moulec, Sylvestre; Besse, Benjamin; Loriot, Yohann; Larroquette, Mathieu; Soubeyran, Isabelle; Toulmonde, Maud; Roubaud, Guilhem; Pernot, Simon; Cabart, Mathilde; Chomy, François; Lefevre, Corentin; Bourcier, Kevin; Kind, Michèle; Giglioli, Ilenia; Sautès-Fridman, Catherine; Velasco, Valérie; Courgeon, Félicie; Oflazoglu, Ezoglin; Savina, Ariel; Marabelle, Aurélien; Soria, Jean-Charles; Bellera, Carine; Sofeu, Casimir; Bessede, Alban; Fridman, Wolf H.; Le Loarer, François; Italiano, Antoine

Online: https://www.nature.com/articles/s43018-021-00232-6

Issue: Nat Cancer. 2021 Aug;2(8):794-802.


Only a minority of patients derive long-term clinical benefit from anti-programmed cell death protein 1 (anti-PD-1) or anti-programmed death-ligand 1 (anti-PD-L1) monoclonal antibodies. The presence of tertiary lymphoid structures (TLSs) has been associated with improved survival in several tumor types. Here, using a large-scale retrospective analysis of three independent cohorts of patients with cancer who were treated with anti-PD-1 or anti-PD-L1 antibodies, we show that the presence of mature TLSs was associated with improved objective response rates, progression-free survival and overall survival, independent of PD-L1 expression status and CD8+ T cell density. These results pave the way for using TLS detection to select patients who are more likely to benefit from immune checkpoint blockade.