2022 World Conference on Lung Cancer (ePosters)-EP16.04-019. Impact of Chemotherapy on Tridimensional Multicellular Non-small Cell Lung Cancer Spheroids With Microenvironment Cells

EP16.04-019. Impact of Chemotherapy on Tridimensional Multicellular Non-small Cell Lung Cancer Spheroids With Microenvironment Cells

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Platinum-based chemotherapy is commonly used in combination with immunotherapy to treat advanced non-small cell lung cancer (NSCLC) patients. However, not all patients benefit from this treatment, highlighting the need for a better understanding of cancer mechanisms and drug resistance. In this study, researchers aimed to develop a model of tridimensional multicellular tumor spheroids (MCTS) to analyze the impact of chemotherapy on NSCLC cells.<br /><br />The researchers used three NSCLC cell lines with varying levels of PD-L1 expression. They created two types of MCTS: simple MCTS containing only tumor cells, and complex MCTS containing both tumor cells and microenvironment cells. The MCTS were treated with repeated chemotherapy drug combinations simulating clinical practice. The impact of chemotherapy was evaluated using viability assays, confocal microscopy, and gene expression analysis.<br /><br />The results showed that chemotherapy decreased MCTS size and cell viability. Fibroblasts in the microenvironment were resistant to chemotherapy, while macrophages were strongly affected. Chemotherapy up-regulated PD-L1 expression in several models of MCTS, depending on baseline PD-L1 expression. This finding was consistent with observations in patients. The researchers also identified modifications in gene expression after treatment, including CD274 (PD-L1), and confirmed PD-L1 up-regulation using flow cytometry and immunohistochemistry.<br /><br />Overall, these findings suggest that MCTS can provide valuable insights into the impact of chemotherapy on tumor cells and the tumor microenvironment. They could be used as non-invasive methods for drug screening. Understanding the mechanisms of drug resistance and the effects of chemotherapy on different cell types within tumors can help improve treatment strategies for NSCLC patients.

Asset Subtitle

Pauline Hulo

Meta Tag

Speaker Pauline Hulo

Topic Tumour Biology and Biomarkers - Tumour Biology & Preclinical Studies

Keywords

Platinum-based chemotherapy

immunotherapy

NSCLC

drug resistance

MCTS

chemotherapy impact

PD-L1 expression

tumor microenvironment

gene expression modifications

treatment strategies