2024 World Conference on Lung Cancer (WCLC) - Posters-P3.06E.04 Genetic and Immunological Backgrounds in Advanced NSCLC Patients Treated with Immunotherapy

P3.06E.04 Genetic and Immunological Backgrounds in Advanced NSCLC Patients Treated with Immunotherapy - NGS and Flow Cytometry Analysis

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This study investigates the genetic and immunological factors affecting the clinical outcomes of advanced non-small-cell lung cancer (NSCLC) patients undergoing first-line immunotherapy or immunochemotherapy. Current reliance on programmed death ligand 1 (PD-L1) expression for outcome prediction is insufficient, necessitating a search for accurate predictive biomarkers.<br /><br />The study involved 20 patients at stage IV NSCLC, treated with pembrolizumab or a combination of pembrolizumab, carboplatin, and pemetrexed. Genetic analysis was conducted using targeted next-generation sequencing (NGS) on DNA from formalin-fixed paraffin-embedded (FFPE) samples, while peripheral blood samples were used for flow cytometry to analyze lymphocyte populations and molecule expression.<br /><br />Results indicated that in short responders (SR), the genes NOTCH4, H3-3A, and KDR were frequently altered, whereas, in long responders (LR), the KDR and TP35 genes were commonly mutated. Notably, a subset of long responders exhibited mutations in the KRAS, NOTCH4, PDGFR, JAK2, and PMS2 genes. Genetic co-occurrences observed included KRAS/STK11 in SR and PMS2/NOTCH4 and PDGFRA/JAK2 in LR groups.<br /><br />Flow cytometry revealed higher baseline percentages of CD4/GATA3 and T regulatory cells among long responders, suggesting these as favorable indicators for progression-free survival (PFS). Specifically, high CD62L expression on CD8 cells and CD4/GATA3 cell percentage correlated positively with PFS.<br /><br />The study concludes that individual genetic alterations deeply influence treatment outcomes, and a single parameter is inadequate for prediction. Multiparametric analyses could lead to identifying biomarkers predictive of responses to anti-PD-1/PD-L1 therapies. Given the limited sample size, further research is essential to validate these findings and enrich understanding of immunotherapeutic response mechanisms.

Asset Subtitle

Paweł Krawczyk

Meta Tag

Speaker Paweł Krawczyk

Topic Pathology & Biomarkers

Keywords

NSCLC

immunotherapy

genetic analysis

biomarkers

pembrolizumab

next-generation sequencing

flow cytometry

PD-L1

CD4/GATA3

KRAS