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(Abstract)

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This study investigated the immunosuppressive environment in the cerebrospinal fluid (CSF) of patients with leptomeningeal metastases (LM) of EGFR mutant non-small cell lung cancer (NSCLC). The authors used single-cell RNA sequencing and ctDNA sequencing to compare the immune microenvironment in LM to brain metastases (BM). They identified unique features in CSF immune cells of LM, including an increase in macrophages and a decrease in T cells. The macrophages in LM were characterized by phenotypic heterogeneity and M2-subtype signatures, with enhanced phagocytosis and angiogenesis functions. The authors found that macrophages in CSF may originate from both the brain and peripheral tissues, with LM macrophages resembling resting microglia and BM macrophages resembling monocytes from the bone marrow. The study also identified midkine (MDK) and its receptors as the most active communication in CSF of LM, with higher levels of MDK in LM compared to BM or normal controls. Patients with higher MDK expression had poorer overall survival. The authors demonstrated that epithelial cells interacted with macrophages and T cells through MDK and its receptors, promoting macrophage M2 polarization and immunosuppressive differentiation. The crosstalk between macrophages and T cells involved TGFB, SPP1-CD44, and CLL17-CCR4, suggesting the recruitment or activation of CD4T cells and Tregs and potential immune escape by the epithelial cells. This study provides insights into the immunosuppressive environment in LM and the role of MDK in promoting tumor progression.

Asset Subtitle

Yang-Si Li

Meta Tag

Speaker Yang-Si Li

Topic Tumor Biology: Translational Biology - IO

Keywords

immunosuppressive environment

cerebrospinal fluid

leptomeningeal metastases

EGFR mutant non-small cell lung cancer

macrophages

T cells

phenotypic heterogeneity

M2-subtype signatures

midkine

overall survival