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-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. Italiano and colleagues demonstrate the utility of mature tertiary lymphoid structures to predict response to immunotherapy, with pathologic analysis in three independent patient cohorts spanning multiple tumor types.

Automated summary

The presence of mature tertiary lymphoid structures is associated with improved response to immunotherapy in cancer patients, predicting objective response rates, progression-free survival, and overall survival. These findings support the potential use of TLS detection to select patients who are more likely to benefit from immune checkpoint blockade.