2023 World Conference on Lung Cancer (Posters)-P1.21. Genetic Susceptibility to Immune Checkpoints Blockade Resistance

Pdf Summary

The study focuses on the genetic susceptibility to immune checkpoint blockade (ICB) resistance in patients with non-small cell lung cancer (NSCLC). The efficacy of ICB treatment, particularly PD-(L)1 antibodies, has been extensively studied, but biomarker development has mainly focused on tumor-related factors. This study explores the host immunologic status and genetic dysregulation as potential factors affecting the response to ICB.<br /><br />The researchers prospectively enrolled 326 NSCLC patients and collected tissue and blood samples from those receiving ICB. A representative set of 60 patients was selected for exome sequencing to characterize the germline contribution to ICB resistance. DNA was extracted from patient samples and processed for sequencing and variant calling. Survival probabilities were estimated, and survival curves were compared using statistical methods.<br /><br />The results showed that 26 germline variants were associated with overall survival (OS) and progression-free survival (PFS), and 52 gene variants were associated with the response to ICB. Univariate analysis revealed that several gene variants were significantly related to survival outcomes. Multivariate analysis identified specific gene variants as independent prognostic factors for OS and PFS, while others were predictive factors for response at 6 months.<br /><br />The researchers concluded that exome sequencing analysis of germline variants could be a suitable approach to identify biomarkers of immune resistance in NSCLC patients. This indicates the potential for genetic factors to influence the response to ICB treatment. Further research in this area could contribute to personalized treatment strategies and improved outcomes for NSCLC patients.<br /><br />In summary, this study sheds light on the role of genetic susceptibility in immune checkpoint blockade resistance in NSCLC patients. The findings highlight the need to explore host immunologic factors and genetic dysregulation as potential biomarkers for ICB response.

Asset Subtitle

Jose Benítez

Meta Tag

Speaker Jose Benítez

Topic Pathology & Biomarkers: Biomarkers for Immuno-oncology

Keywords

genetic susceptibility

immune checkpoint blockade resistance

non-small cell lung cancer

NSCLC

ICB treatment

PD-(L)1 antibodies

biomarker development

tumor-related factors

host immunologic status

genetic dysregulation