2023 Targeted Therapies of Lung Cancer Meeting (Poster)-P1.10. Impact of Aneuploidy and Chromosome 9p Loss on Tumor Immune Microenvironment and Immune Checkpoint Inhibitor Efficacy in Non-small Cell Lung Cancer

P1.10. Impact of Aneuploidy and Chromosome 9p Loss on Tumor Immune Microenvironment and Immune Checkpoint Inhibitor Efficacy in Non-small Cell Lung Cancer

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This study investigates the impact of aneuploidy burden and chromosomal arm-level events on the efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). The researchers included patients who received a PD-(L)1 inhibitor alone or in combination with a CTLA-4 inhibitor at two academic centers. They quantified aneuploidy using the adjusted fraction of chromosomal arm alterations (FAA) and determined arm-level events in samples with adequate sequencing coverage. They found that NSCLCs with high aneuploidy and chromosome 9p loss had a distinct tumor immune microenvironment and less favorable outcomes to ICIs. The FAA increased with advanced cancer stage and decreased with higher PD-L1 tumor proportion score levels. There was a weak correlation between FAA and tumor mutational burden. The study also analyzed the impact of 9p loss on ICI efficacy and found that NSCLCs with 9p loss had lower objective response rates, shorter progression-free survival, and shorter overall survival compared to those without 9p loss. Additionally, tumors with high FAA levels or chromosome 9p loss had fewer tumor-associated immune cells. These findings suggest that aneuploidy burden and chromosome 9p loss may serve as potential biomarkers for predicting ICI efficacy in NSCLC. Further studies are needed to validate these findings and understand the underlying mechanisms.

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Joao Alessi, Dana-Farber Cancer Institute, United States

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Speaker Joao Alessi, Dana-Farber Cancer Institute, United States

Topic Poster Listing

Keywords

aneuploidy burden

chromosomal arm-level events

immune checkpoint inhibitors

non-small cell lung cancer

PD-(L)1 inhibitor

CTLA-4 inhibitor

chromosome 9p loss

tumor immune microenvironment

tumor mutational burden

biomarkers