Immunomodulatory Molecules On Lung Cancer Stem Cells From Lymph Nodes Aspirates

Area of Science:

• Immunology
• Oncology
• Cancer Biology

Background:

• Immune checkpoint inhibitors have transformed non-small cell lung cancer (NSCLC) treatment, but not all patients respond.
• PD-L1 expression on tumor cells is the sole approved biomarker, prompting research into additional biomarkers.
• Understanding the tumor microenvironment and cell-surface molecules is crucial for improving NSCLC therapy.

Purpose of the Study:

• To analyze immunomodulatory molecules (PD-L1, CD47, CD73, Fas, FasL) on mature tumor cells (MTCs) and cancer stem cells (CSCs) in lymph node (LN) aspirates.
• To correlate these findings with lymphocyte subpopulations in peripheral blood (PB) of NSCLC patients.
• To identify potential biomarkers associated with NSCLC metastasis and immune evasion.

Main Methods:

• Collected peripheral blood (PB) and lymph node (LN) aspirates from 20 NSCLC patients via endobronchial ultrasound-guided transbronchial needle aspiration (EBUS/TBNA).
• Utilized multiparameter flow cytometry to analyze the expression of PD-L1, CD47, CD73, Fas, and FasL on MTCs and CSCs.
• Correlated cell surface molecule expression with lymphocyte subpopulations (PD-1+ CD8 T cells, Fas+ CD8 T cells) in PB and LNs.

Main Results:

• Higher frequencies of MTCs and CSCs expressing immunomodulatory molecules were observed in metastatic LNs compared to non-metastatic LNs.
• CSCs exhibited significantly higher expression of CD47 and PD-L1 than MTCs.
• Increased frequencies of PD-1+ CD8 T cells and Fas+ CD8 T cells were found in the PB of patients with confirmed metastases.
• FasL+ MTCs correlated with Fas+ CD3 T cells in LNs and Fas+ CD8 T cells in PB.
• Patients with metastatic disease showed a significantly higher FasL+/Fas+ MTCs ratio.

Conclusions:

• Both MTCs and CSCs express diverse immunomodulatory molecules, suggesting multifaceted roles in immune evasion.
• The frequency of FasL+ MTCs is associated with altered lymphocyte distribution in LNs and PB.
• These findings highlight potential novel biomarkers for NSCLC metastasis and immune response, warranting further investigation for therapeutic targeting.