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Updated: Oct 25, 2025
Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression
Published on: January 19, 2019
Prognostic value of Thyroid Transcription Factor-1 expression in lung adenocarcinoma in patients treated with anti
Loïck Galland1,2,3, Anne Laure Le Page4, Julie Lecuelle1,3
1Platform of Transfer in Biological Oncology, Georges François Leclerc Cancer Center - UNICANCER, Dijon, France.
Abstract:
Anti-PD1/PD-L1-directed immune checkpoint inhibitors are game changers in advanced non-small-cell lung cancer, but biomarkers are lacking. The aim of our study was to find clinically relevant biomarkers of the efficacy of ICI in non-squamous NSCLC. We conducted a retrospective study of patients receiving ICI for advanced non squamous NSCLC in two cohorts. For a subset of patients, RNAseq data were generated on tumor biopsy taken before ICI. The primary end point was progression-free survival under ICI. Secondary end point was overall survival from ICI initiation. In the cohort, we studied 231 patients. Clinico-pathological characteristics included KRAS mutant status (n = 88), TTF1-positive expression (n = 136), LIPI (Lung Immune Prognostic Index) score of 0 (n = 116). In our cohort, lack of TTF1 expression, LIPI score >0, line of treatment >1, and liver metastases were associated with poorer PFS. TTF1 and PD-L1 status could be used to stratify survival and improve the AUC for prediction of prognosis in comparison with the PD-L1 gold standard. Using an external cohort of 154 patients, we confirmed the independent prognostic role of TTF1. TTF1 expression and PD-L1 can be used to stratify risk and predict PFS and OS in patients treated with ICI for NS-NSCLC.
Insights
Biomarkers like TTF1 expression and PD-L1 status can predict treatment effectiveness in advanced non-squamous non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). These markers help stratify patient risk and forecast progression-free survival (PFS) and overall survival (OS).
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Discovery
Background:
- Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have transformed advanced non-small cell lung cancer (NSCLC) treatment.
- Effective biomarkers are critically needed to guide ICI therapy in NSCLC, particularly in non-squamous subtypes.
Purpose of the Study:
- To identify clinically relevant biomarkers predicting the efficacy of ICI treatment in advanced non-squamous NSCLC.
- To evaluate the prognostic value of TTF1 expression and PD-L1 status in NSCLC patients undergoing ICI therapy.
Main Methods:
- Retrospective analysis of 231 patients with advanced non-squamous NSCLC treated with ICIs, with RNAseq data for a subset.
- Assessment of progression-free survival (PFS) and overall survival (OS) as primary and secondary endpoints.
- Validation using an external cohort of 154 patients.
Main Results:
- Lack of TTF1 expression, a high Lung Immune Prognostic Index (LIPI) score, later lines of treatment, and liver metastases were associated with poorer PFS.
- TTF1 and PD-L1 status demonstrated potential to stratify survival and improve prognostic prediction accuracy compared to PD-L1 alone.
- The independent prognostic role of TTF1 was confirmed in an external validation cohort.
Conclusions:
- TTF1 expression and PD-L1 status are valuable biomarkers for risk stratification and predicting PFS and OS in patients with non-squamous NSCLC treated with ICIs.
- Integrating TTF1 and PD-L1 assessment can enhance personalized treatment strategies for advanced NSCLC.
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