2024 World Conference on Lung Cancer (WCLC) - Posters-P3.13D.07 Longitudinal Tumor Microenvironment Analysis in Extensive Stage SCLC Patients Treated with Dual Checkpoint Inhibitor Blockade

P3.13D.07 Longitudinal Tumor Microenvironment Analysis in Extensive Stage SCLC Patients Treated with Dual Checkpoint Inhibitor Blockade

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This study investigates the tumor microenvironment (TME) and immune response in small cell lung cancer (SCLC) patients treated with a combination of nivolumab and ipilimumab, dual checkpoint inhibitors. SCLC is a highly aggressive cancer with limited effective treatment options and a poor prognosis. The research primarily focused on understanding dynamic changes in TME and identifying potential predictive biomarkers for immunotherapy response.<br /><br />Key findings from this phase 2 clinical trial (NCT03670056) include a significant increase in tumor-infiltrating lymphocytes (TILs), particularly CD8 and CD4 T cells, after treatment. This increase was more pronounced in patients exhibiting clinical activity, defined as partial or stable disease, compared to those with progressive disease. Notably, TIL levels declined to baseline measures at disease progression.<br /><br />Another interesting observation was the correlation between the transition:transversion (Ti:Tv) ratio of genetic mutations and clinical response. Patients showing clinical activity had lower Ti:Tv ratios at week 4 than those without, suggesting a link between genomic changes and immune activation.<br /><br />Gene expression analyses revealed distinct RNA profiles between patients with and without clinical response. Pathways related to T-cell activation and inflammation were enriched in those responding to the treatment, indicating potential biomarkers for monitoring and predicting treatment outcomes.<br /><br />The study highlights the necessity for further research to explore the resistance mechanisms and response characteristics in SCLC. Validation of the identified biomarkers through comprehensive clinical and experimental models is recommended to enhance therapeutic strategies for this aggressive cancer.

Asset Subtitle

Anne Chiang

Meta Tag

Speaker Anne Chiang

Topic SCLC & Neuroendocrine Tumors

Keywords

tumor microenvironment

immune response

small cell lung cancer

nivolumab

ipilimumab

checkpoint inhibitors

tumor-infiltrating lymphocytes

predictive biomarkers

gene expression

T-cell activation