2023 World Conference on Lung Cancer (Posters)-P1.09. Midkine Dependent Immunosuppressive Environment in Cerebrospinal Fluid May Promote Leptomeningeal Metastases of EGFR Mutant NSCLC

P1.09. Midkine Dependent Immunosuppressive Environment in Cerebrospinal Fluid May Promote Leptomeningeal Metastases of EGFR Mutant NSCLC - PDF(Slides)

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Leptomeningeal metastases (LM) are a severe complication of non-small cell lung cancer (NSCLC), especially after resistance to the drug Osimertinib. In this study, the researchers aimed to investigate the immune microenvironment of LM and its potential role in Osimertinib resistance. Clinical data from 784 cases of LM were analyzed retrospectively, and cerebrospinal fluid (CSF) samples were collected from 10 NSCLC patients with LM or brain metastases for single-cell RNA sequencing.<br /><br />The analysis revealed that the immune cell profile in the CSF of LM was different from that in brain metastases, with increased levels of macrophages and decreased levels of T cells. Macrophages in the CSF of LM displayed heterogeneity and exhibited enhanced immunosuppressive properties and activation of adaptive tumor immunity.<br /><br />A unique subtype of macrophages, called RNASE1_M, was found to be associated with Osimertinib resistance and LM development. These macrophages were potentially regulated by a protein called MDK, which was significantly elevated in the CSF of LM compared to brain metastases. The high levels of MDK were also associated with poorer outcomes in LM patients. Additionally, interactions between epithelial cells and macrophages, mediated by the CD47-SIRPA pathway, were identified.<br /><br />The study provides insights into the immune microenvironment of LM in NSCLC patients and its relationship with Osimertinib resistance. The RNASE1_M subtype of macrophages, regulated by MDK, emerges as a potential target for therapeutic interventions to overcome LM. Further research is needed to validate these findings and develop effective strategies for treating LM in NSCLC patients.

Asset Subtitle

Yang-Si Li

Meta Tag

Speaker Yang-Si Li

Topic Tumor Biology: Translational Biology - IO

Keywords

Leptomeningeal metastases

non-small cell lung cancer

Osimertinib resistance

immune microenvironment

clinical data

cerebrospinal fluid

single-cell RNA sequencing

macrophages

T cells

RNASE1_M subtype