Abstract
IntroductionCancer 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.MethodsLNs’ 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.ResultsPD-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.ConclusionThe 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.
Highlights
Cancer stem cells (CSCs) are implicated in tumor initiation and development of metastasis
CSCs, and progressive disease (PD)-L1+ CSCs were much higher in frequency in metastatic than in non-metastatic lymph nodes (LNs)
Considering PD-L1+ CSCs, we found that the PD-L1+ CSCs positively correlated with the percentage of C D8+ T cells (r = 0.6225, p = 0.0298), Tregs (r = 0.6257, p = 0.0280), PD-1+ CD4+ T cells (r = 0.6474, p = 0.0233), and Tim3+ CD4+ T cells (r = 0.6161, p = 0.0198)
Summary
Cancer stem cells (CSCs) are implicated in tumor initiation and development of metastasis. 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. Cancer Immunology, Immunotherapy (2021) 70:453–461 this cross-talk between CSCs and other cells within the TME as well as interactions of CSCs with the immune system is not fully understood. Immunotherapy has been developed to strengthen cancer immunosurveillance These monoclonal antibodies targeting checkpoint molecules PD-1 and PD-L1 have been especially effective in lung cancer. The presence of PD-L1+ CSCs in metastatic LNs in lung cancer patients was confirmed, which may suggest their importance in the cross-talk with PD-1+ immune cells and immunosuppressive properties [11]
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