2022 World Conference on Lung Cancer (ePosters)-EP16.04-015. Chemotherapy Upregulates Programmed Cell Death Ligand 1 Expression in Non-Small Cell Lung Cancer Cell Lines and Patient-Derived Organoid Models

EP16.04-015. Chemotherapy Upregulates Programmed Cell Death Ligand 1 Expression in Non-Small Cell Lung Cancer Cell Lines and Patient-Derived Organoid Models

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A study was conducted to investigate whether chemotherapy can enhance the effectiveness of anti-PD-1/PD-L1 therapy in non-small cell lung cancer (NSCLC) tumors by inducing PD-L1 expression through the activation of the cGAS-STING pathway. The researchers treated NSCLC cell lines and patient-derived organoids with cisplatin, a chemotherapeutic drug, and observed an upregulation of PD-L1 expression. This increase in PD-L1 expression was sustained even after a drug-free period of 72 hours. The study also found that chemotherapy activates the cGAS-STING pathway in NSCLC cell lines. Furthermore, the expression of cGAS was found to correlate with various immune markers in NSCLC patients, suggesting a potential role of cGAS in regulating PD-L1 expression. <br /><br />The clinical efficacy of PD-1/PD-L1 inhibitor therapy in NSCLC patients is known to be higher in tumors with high PD-L1 expression. However, combining anti-PD1/PDL1 with chemotherapy has shown greater clinical efficacy even in patients with low PD-L1 expression tumors. The study provides insights into the mechanisms through which chemotherapy can enhance the effectiveness of anti-PD-1/PD-L1 therapy in NSCLC by upregulating PD-L1 expression via the cGAS-STING pathway. This knowledge can potentially guide the development of more effective treatment strategies for NSCLC patients. The research was funded by CIHR, the Princess Margaret Cancer Foundation, and the University of Toronto School of Graduate Studies Travel Grant.<br /><br />In conclusion, chemotherapy with cisplatin upregulates PD-L1 expression in NSCLC cell lines and patient-derived organoids, and this upregulation is sustained even after drug discontinuation. The activation of the cGAS-STING pathway by chemotherapy may play a role in regulating PD-L1 expression. Further studies are needed to fully understand the potential of combining chemotherapy with anti-PD-1/PD-L1 therapy in NSCLC treatment.

Asset Subtitle

Maryam Khalil

Meta Tag

Speaker Maryam Khalil

Topic Tumour Biology and Biomarkers - Tumour Biology & Preclinical Studies

Keywords

chemotherapy

anti-PD-1/PD-L1 therapy

non-small cell lung cancer

NSCLC

tumors

PD-L1 expression

cGAS-STING pathway

cisplatin

upregulation

immune markers