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

Nat Cancer. 2021 Aug;2(8):794-802. doi: 10.1038/s43018-021-00232-6. Epub 2021 Aug 12.


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.

Keywords: Immune checkpoint inhibitors; biomarkers; tertiary lymphoid structures (TLS); tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • B7-H1 Antigen / therapeutic use
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Lung Neoplasms* / drug therapy
  • Retrospective Studies
  • Tertiary Lymphoid Structures*


  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • Immune Checkpoint Inhibitors