2024 World Conference on Lung Cancer (WCLC) - Posters-P1.03D.07 Overcoming Immunotherapy Resistance in Non-Small Cell Lung Cancer With a Triple Combination Therapy: Efficacy and Mechanisms

P1.03D.07 Overcoming Immunotherapy Resistance in Non-Small Cell Lung Cancer With a Triple Combination Therapy: Efficacy and Mechanisms

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The study explores the potential of a triple combination therapy to overcome immunotherapy resistance in advanced non-small cell lung cancer (NSCLC). Despite the effectiveness of anti-programmed death receptor-1 (PD-1) antibody in cancer treatment, its success rate as a standalone therapy for advanced NSCLC remains limited to about 20%. This study specifically investigates the combined use of hypofractionated radiotherapy, anti-PD-1, and anti-T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) antibody.<br /><br />Research was conducted with 51 NSCLC patients showing resistance to immunotherapy; they received hypofractionated radiotherapy targeting lung lesions. Additionally, five patients with locally advanced NSCLC were treated with a combination of radiotherapy, anti-PD-1, and anti-TIGIT antibodies. In parallel, preclinical models involved mouse tumor studies using similar combination treatments. Analysis through flow cytometry, immunohistochemistry, and RNA sequencing pointed out significant enhancements in immune cell infiltration and antitumor responses due to the combined therapy. This included improved tumor-associated macrophage dynamics and observed abscopal effects, which denote the beneficial impacts of localized treatment beyond the targeted area.<br /><br />Results indicated that the triple therapy could effectively engage various immune-related pathways, providing substantive antitumor immune responses and ameliorating resistance to immunotherapy. The empirical evidence showed a partial response in all evaluated patients, suggesting this strategy's promise in clinical settings.<br /><br />The study calls for further investigation into the molecular mechanisms of this combination therapy and for future clinical trials to validate its efficacy and safety in larger cohorts of advanced NSCLC patients. If successful, this combined therapy approach could represent a novel strategy for overcoming resistance to current immunotherapy regimens in NSCLC.

Asset Subtitle

Yaping Xu

Meta Tag

Speaker Yaping Xu

Topic Tumor Biology – Translational Biology

Keywords

triple combination therapy

immunotherapy resistance

non-small cell lung cancer

NSCLC

anti-PD-1 antibody

hypofractionated radiotherapy

anti-TIGIT antibody

immune cell infiltration

antitumor responses

abscopal effects