2024 World Conference on Lung Cancer (WCLC) - Posters-P1.06B.13 Blood-Based Loss of Heterozygosity in Human Leukocyte Antigen Class I Alleles Reveals Resistance to Immunotherapy in Non-Small Cell Lung Cancer

P1.06B.13 Blood-Based Loss of Heterozygosity in Human Leukocyte Antigen Class I Alleles Reveals Resistance to Immunotherapy in Non-Small Cell Lung Cancer

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This study investigates the role of blood-based Loss of Heterozygosity in Human Leukocyte Antigen Class I (bHLA-LOH) as a biomarker for immune evasion and its implications on treatment resistance in non-small cell lung cancer (NSCLC). The researchers analyzed 516 paired tissue-blood NSCLC specimens (GPD cohort) to identify bHLA-LOH characteristics and further examined its status in 58 advanced NSCLC patients receiving immunotherapy (NCC cohort).<br /><br />Key findings include the detection rates in the GPD cohort of tissue-based HLA-LOH (tHLA-LOH) in 46.1% and bHLA-LOH in 14.9% of patients. This indicates a lower occurrence in blood samples compared to tissue samples. bHLA-LOH is significantly associated with specific clinical characteristics such as gender and smoking status. In particular, it was more prevalent in males and those with a history of smoking.<br /><br />Moreover, bHLA-LOH was linked with increased blood-based tumor mutational burden (bTMB), neoantigens, and intra-tumor heterogeneity, suggesting these factors might contribute to its role in immunotherapy resistance. In the NCC cohort, patients with baseline bHLA-LOH displayed inferior responses to immunotherapy, showing shorter median progression-free survival (mPFS) and overall survival (mOS) than non-bHLA-LOH patients.<br /><br />The study concludes that bHLA-LOH can serve as a useful, non-invasive biomarker for predicting primary and acquired resistance to immunotherapy in NSCLC. This highlights its potential in guiding clinical decisions and underscores the need for further clinical trials to solidify its use as a predictive tool. By offering insights into immune evasion mechanisms, bHLA-LOH might help tailor more effective treatment strategies for these patients.

Asset Subtitle

Yiting Dong

Meta Tag

Speaker Yiting Dong

Topic Pathology & Biomarkers

Keywords

bHLA-LOH

biomarker

immune evasion

treatment resistance

NSCLC

immunotherapy

tumor mutational burden

neoantigens

intra-tumor heterogeneity

clinical trials