PD-L1+ lung cancer stem cells modify the metastatic lymph-node immunomicroenvironment in nsclc patients

Abstract

Introduction Cancer stem cells (CSCs) are implicated in tumor initiation and development of metastasis. However, whether CSCs also affect the immune system is not fully understood. We investigated correlations between the PD-L1 + CSCs, changes in T-cell phenotype in metastatic and non-metastatic lymph nodes (LNs) and response to treatment. Methods LNs' aspirates were obtained during the EBUS/TBNA procedure of 20 NSCLC patients at different stages of the disease. CSCs and T-cell characteristics were determined by flow cytometry. Results PD-L1 + CSCs positively correlated with the percentage of Tregs, PD-1 + CD4 T cells and Tim3 + CD4 + T cells, whereas PD-L1 + CSCs were negatively correlated with CD4 + T cells and CD28 + CD4 + T cells. The percentage of PD-L1 + CSCs was higher in patients with progressive disease (PD) as compared to patients with stable disease (SD) or partial response (PR). Among T cells, only PD-1 + CD4 + T cells and Tim3 + CD4 + T-cell frequencies were higher in patients with PD as compared to patients with SD or PR. Conclusion The frequency of PD-L1 + CSCs associates with an altered T-cell frequency and phenotype indicating that CSCs can affect the immune system. The higher percentage of PD-L1 + CSCs in patients with PD may confirm their resistance to conventional therapy, suggesting that CSCs may be an interesting target for immunotherapy.

Immune- and Stemness-Related Genes Revealed by Comprehensive Analysis and Validation for Cancer Immunity and Prognosis and Its Nomogram in Lung Adenocarcinoma

“…CSC can evade immune surveillance due to their immunomodulatory effects ( 10 ). CSCs also can affect the immune system, such as the immune microenvironment of tumor lymph nodes ( 11 ). However, anti-cancer therapies currently not only fail to eradicate CSC clones but also assist in the screening of resistant CSC clones from the CSC pool, leading to treatment resistance and relapse ( 5 , 12 ).…”

Current treatments for non-small cell lung cancer

“…More specifically, targeting signaling pathways such as Wnt, hippo, and notch could inhibit the stemness of cancer cells or the biomarkers correlated with CSCs (71). CSCs also exist in NSCLC, and lung cancers also have the feature of stemness; therefore, these facts confirm that targeting CSCs in NSCLC is crucial (72,73).…”

A Combination of Cytokine-Induced Killer Cells With PD-1 Blockade and ALK Inhibitor Showed Substantial Intrinsic Variability Across Non-Small Cell Lung Cancer Cell Lines

“…The authors showed that both CD133 and CD87 are expressed in the SBC-7 cell line as inadequate markers of CSCs and might be beneficial for predicting chemotherapy resistance. Recently, a study confirmed the identification of CSCs and showed that PD-L1 + CSCs are strongly associated with altered T cell phenotypes and, in particular, the frequency of regulatory molecule-expressing T cells in metastatic lymph nodes of NSCLC patients ( 50 ). Of note, our current study mainly concerns enhancing the cytotoxicity and did not emphasize CSCs; however, we cannot exclude the contribution of lung cancer associated CSCs.…”