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Updated: Oct 4, 2025
Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of
Lucile Vanhersecke1,2, Maxime Brunet2,3, Jean-Philippe Guégan4
1Department of Pathology, Institut Bergonié, Bordeaux, France.
Abstract:
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.
Insights
Tertiary lymphoid structures (TLS) presence predicts better outcomes for cancer patients receiving anti-PD1/PD-L1 therapies. Detecting mature TLS can help identify patients likely to benefit from immune checkpoint blockade, improving treatment selection.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Anti-PD1/PD-L1 monoclonal antibodies offer limited long-term clinical benefit to many cancer patients.
- Tertiary lymphoid structures (TLS) have shown potential as biomarkers for improved survival in various cancers.
Purpose of the Study:
- To investigate the association between mature tertiary lymphoid structures (TLS) and clinical outcomes in cancer patients treated with anti-PD1/PD-L1 antibodies.
- To determine if TLS presence can predict response to immune checkpoint blockade independently of other biomarkers.
Main Methods:
- Retrospective analysis of three independent cohorts of cancer patients.
- Evaluation of mature TLS presence in tumor tissues.
- Correlation analysis with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS).
Main Results:
- The presence of mature TLS was significantly associated with improved ORR, PFS, and OS.
- This association remained significant regardless of PD-L1 expression status and CD8+ T-cell density.
- Mature TLS emerged as a robust predictive biomarker for anti-PD1/PD-L1 therapy efficacy.
Conclusions:
- Mature tertiary lymphoid structures are a promising biomarker for predicting patient response to anti-PD1/PD-L1 therapy.
- TLS detection can aid in selecting patients who are most likely to benefit from immune checkpoint blockade.
- Incorporating TLS assessment into clinical practice may optimize immunotherapy treatment strategies.
