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


Nature cancer, August 2021

Lucile Vanhersecke, Maxime Brunet, Jean-Philippe Guégan, Christophe Rey, Antoine Bougouin , Sophie Cousin , Sylvestre Le Moulec, Benjamin Besse, Yohann Loriot, Mathieu Larroquette, Isabelle Soubeyran , Maud Toulmonde , Guilhem Roubaud , Simon Pernot , Mathilde Cabart, François Chomy , Corentin Lefevre, Kevin Bourcier , Michèle Kind, Ilenia Giglioli, Catherine Sautès-Fridman , Valérie Velasco , Félicie Courgeon, Ezoglin Oflazoglu, Ariel Savina , Aurélien Marabelle  , Jean-Charles Soria, Carine Bellera, Casimir Sofeu, Alban Bessede4, Wolf H. Fridman , François Le Loarer  and Antoine Italiano



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.