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.