WCLC 2025 - Posters & ePosters-EP.06.44 Tertiary Lymphoid Structures in the Tumor Micro Immune Environment of EGFR Positive Lung Cancer Are Associated Prognosis

EP.06.44 Tertiary Lymphoid Structures in the Tumor Micro Immune Environment of EGFR Positive Lung Cancer Are Associated Prognosis

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This study by Yamaguchi et al. investigates the role of tertiary lymphoid structures (TLS) within the tumor microenvironment (TME) of EGFR-positive non-small cell lung cancer (NSCLC) and their association with prognosis. TLS are lymphoid aggregates containing PNAd-positive high endothelial venules, implicated in enhancing anti-tumor immune responses. Prior findings linked TLS with favorable outcomes in NSCLC, but their role in EGFR-mutant lung cancer, specifically Exon19 deletion (Exon19del) and L858R mutations, remained unclear.<br /><br />The retrospective study analyzed surgical cases from 2007-2015, assessing TLS density via immunohistochemistry and spatial proteomics with imaging mass cytometry (Hyperion XTi). TLS levels were categorized as low (0–5 per 10 high-power fields) or high (≥6).<br /><br />Key findings include: TLS was predominantly elevated in L858R-mutant tumors compared to Exon19del (57% vs. 37%, p=0.009). High TLS expression correlated with significantly lower recurrence rates overall (p=0.028), especially in stage II-IV patients (p=0.004) and L858R cases (p=0.001). Progression-free survival following EGFR-tyrosine kinase inhibitor (TKI) treatment was also improved in high TLS expressers (p=0.045). Multivariate analysis identified both pathological stage and TLS level as independent prognostic factors.<br /><br />Spatial proteomics revealed that high TLS tumors exhibited distinct immune cell localization, including elevated granzyme-B expression, indicating active cytotoxic immune responses contributing to tumor cell damage. The study suggests TLS may enhance immune activation and improve response to therapies such as ICIs and TKIs, with L858R EGFR mutations showing a stronger relationship with TLS presence.<br /><br />In conclusion, TLS represent a novel prognostic biomarker in EGFR-mutant NSCLC, especially in L858R cases, potentially modulating therapeutic efficacy through immune environment alterations. This supports further exploration of TLS in tailoring immunotherapeutic strategies for EGFR-positive lung cancer patients.<br /><br />No conflicts of interest were declared.

Asset Subtitle

Hikaru Yamaguchi

Meta Tag

Speaker Hikaru Yamaguchi

Topic Pathology and Biomarkers

Keywords

tertiary lymphoid structures

TLS

EGFR-positive non-small cell lung cancer

NSCLC

L858R mutation

Exon19 deletion

tumor microenvironment

immune response

prognostic biomarker

EGFR-tyrosine kinase inhibitor