Analyzing pretreatment tumor samples from patients receiving anti-PD-1/PD-L1 therapy, Vanhersecke and Brunet et al. evaluated whether the presence of mature tertiary lymphoid structures (mTLS) could predict therapeutic response. Identified through immunofluorescence, roughly 1/4 of patients had mTLS featuring B/T cells and follicular DCs. Compared to mTLS- patients, mTLS+ patients had improved objective response, progression-free survival, and overall survival, regardless of PD-L1 expression. TLS status correlated with CD8+ T cell density, but more strongly predicted response than CD8+ T cell density, PD-L1 status, or mutational burden.
Contributed by Alex Najibi
ABSTRACT: 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.
Author Info: (1) Department of Pathology, Institut Bergonié, Bordeaux, France. (2) Faculty of Medicine, University of Bordeaux, Bordeaux, France. (3) Department of Medicine, Institut Bergonié,
Author Info: (1) Department of Pathology, Institut Bergonié, Bordeaux, France. (2) Faculty of Medicine, University of Bordeaux, Bordeaux, France. (3) Department of Medicine, Institut Bergonié, Bordeaux, France. (4) Explicyte Immuno-Oncology, Bordeaux, France. (5) Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Equipe Labellisée Ligue Nationale Contre le Cancer, USPC Université de Paris, Paris, France. 6Department of Oncology, Clinique Marzet, Pau, France. (7) Department of Medicine, Gustave Roussy, Villejuif, France. (8) Department of Radiology, Institut Bergonié, Bordeaux, France. (9) AstraZeneca, Rahway, NJ, USA. (10) Clinical Research and Clinical Epidemiology Unit (ISO 9001 Certified), Institut Bergonié, Comprehensive Cancer Centre, Bordeaux, France. (11) These authors contributed equally: Lucile Vanhersecke, Maxime Brunet, Alban Bessede, Wolf H. Fridman, François Le Loarer, Antoine Italiano.
