Immunomodulatory Molecules On Lung Cancer Stem Cells From Lymph Nodes Aspirates

Abstract

Over the past decade, immune checkpoint inhibitors have revolutionized the treatment of non-small cell lung cancer (NSCLC). Unfortunately, not all patients benefit from PD-(L)1 blockade, yet, the PD-L1 tumor cell expression is the only approved biomarker, and other biomarkers have been investigated. In the present study, we analyzed the presence of immunomodulatory molecules: PD-L1, CD47, CD73, Fas, and FasL on mature tumor cells (MTCs) and cancer stem cells (CSCs) in lymph nodes (LNs) aspirates and refer it to the lymphocyte subpopulation in peripheral blood (PB). PB samples and LNs aspirates obtained during the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS/TBNA) procedure of 20 patients at different stages of NSCLC. The cells were analyzed by multiparameter flow cytometry. We reported the higher frequency of MTCs and CSCs expressing the investigated immunomodulating molecules in metastatic LNs than in nonmetastatic. The expression of CD47 and PD-L1 was significantly higher on CSCs than on MTCs. Among the lymphocyte subpopulation in PB, we observed a higher frequency of PD-1+ CD8 T cells and Fas+ CD8 T cells in patients with confirmed metastases than in nonmetastatic. Next, we found that the percentage of FasL+ MTCs correlated with the frequency of Fas+ CD3 T cells in LNs aspirates and Fas+ CD8 T cells in PB. Finally, we found that patients with metastatic disease had a significantly higher FasL+/Fas+ MTCs ratio than patients with nonmetastatic disease. Both MTCs and CSCs express different immunomodulatory molecules on their surface. The frequency of FasL+ MTCs associates with altered distribution of Fas+ lymphocyte subpopulations in LNs and PB.

Effector Memory T Cells and CD45RO+ Regulatory T Cells in Metastatic vs. Non-Metastatic Lymph Nodes in Lung Cancer Patients

“…Other researchers confirm the presence of effector lymphocytes at the site of the ongoing neoplastic process and their prognostic importance. Our present and former findings indicate specificity of the character of the environment of the metastatic tumor site ( 52 – 55 ). The high number of CD8+ CD45RO+ effector memory T cells found in the primary tumor lesion significantly correlates with a positive clinical outcome in various cancers.…”

CD47: The Next Frontier in Immune Checkpoint Blockade for Non-Small Cell Lung Cancer

“…Functionally, CD47 blockade using anti-CD47 or anti-SIRPα mAb significantly increased macrophage phagocytosis of LCSC isolated from NSCLC cell lines and patient tumors. A second study that investigated immunomodulatory molecules in LCSC obtained from lymph node aspirates, confirmed that CD47 expression was higher on cancer stem cells compared to mature tumor cells [241]. These findings may suggest that CD47 has a role in maintaining the stem cell compartment in NSCLC.…”

Estrogens, Cancer and Immunity

“…However, observational studies do not indicate any significant differences in PD-L1 expression between men and women [122], which was confirmed in some of our studies. We explored immune cell phenotypes and expression of immune checkpoints of immune cells derived from the blood and TME of lung cancer patients [123]. When analyzing differences between sex, we did not find spectacular results.…”