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

Only a minority of patients derive long-term clinical benefit from anti-PD1/PD-L1 monoclonal antibodies. The presence of tertiary lymphoid structures (TLS) has been associated with improved survival in several tumor types. Here, using a large-scale retrospective analysis of three independent cohorts of cancer patients treated with anti-PD1/PD-L1 antibodies, we showed that the presence of mature TLS was associated with improved objective response rate, progression-free survival, and overall survival independently 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.

Déclaration de conflit d'intérêts

DECLARATION OF INTERESTS LV, MB, SC, SLM, ML, IS, MT, GR, SP, MC, FC, CL, KB, MK, IG, CSF, VV, FC, WHF, and FLL: Nothing to disclose AB, JPG, and CR: Employees of Immusmol/Explicyte EO, AS: Employees of Astra Zeneca AI: Received research grants from Astra Zeneca, Bayer, BMS, Chugai, Merck, MSD, Pharmamar, Novartis, Roche, and received personal fees from Epizyme, Bayer, Lilly, Roche, and Springworks BB: Received grants from AstraZeneca , Pfizer , Eli Lilly , Onxeo , Bristol Myers Squibb , Inivata , Abbvie , Amgen , Blueprint Medicines , Celgene , GlaxoSmithKline , Ignyta , Ipsen , Merck KGaA , MSD Oncology , Nektar , PharmaMar , Sanofi , Spectrum Pharmaceuticals , Takeda , Tiziana Therapeutics , Cristal Therapeutics , Daiichi Sankyo , Janssen Oncology , OSE Immunotherapeutics , BeiGene , Boehringer Ingelheim , Genentech , SERVIER , Tolero Pharmaceuticals YL: Received grants and personal fees from Janssen, during the conduct of the study; personal fees and non-financial support from Astellas, grants and personal fees from Sanofi, personal fees and non-financial support from Roche, personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from MSD, personal fees and non-financial support from BMS, personal fees from Clovis , personal fees and non-financial support from Seattle Genetics, personal fees from Incyte, personal fees from Pfizer. AM: Received research grants from Mersu, Bristol-Myers Squibb, Boehringer Ingelheim, Transgene, MSD and received personal fees from Bristol-Myers Squibb, AstraZeneca, MedImmune, Oncovir, Merieux JCS: Has received consultancy fees from AstraZeneca, Astex, Clovis, GSK, GamaMabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, Pharma Mar, Pierre Fabre, Roche/Genentech, Sanofi, Servier, Symphogen, and Takeda.