129P Regulatory dendritic cells correlate with an altered T cell distribution and regulatory T cell phenotype in metastatic lymph nodes of NSCLC patients

Abstract

Dendritic cells (DCs) are considered to be the most important professional population of antigen-presenting cells and play a crucial role in the activation of the immune system. However, the proper function of DCs is altered by the tumor microenvironment (TME). Despite the progress in anticancer immunotherapy, there are still many unresolved issues. Among them, the immunomodulatory properties of DCs in lung cancer are of interest. The aim of the study was to analyze the PD-1+ PD-L1+ CD80- DCs subset, described as regulatory dendritic cells (DCregs), and to investigate correlations between the presence of DCregs and changes in T cell frequencies and immunomodulatory molecules in metastatic and non-metastatic lymph nodes (LNs) aspirates of NSCLC patients. LNs aspirates were obtained during the diagnostic EBUS TBNA procedure of 30 NSCLC patients. DCregs and T cell characteristics were determined by multiparameter flow cytometry. We noticed a higher percentage of DCregs in the metastatic than in the non-metastatic LNs (22.5% vs. 3.1%). DCs cells show increased expression of PD-1 and PD-L1. Additionally, metastatic LNs contained a lower percentage of CD4 T cells, whereas the percentage of CD8 T cells and Tregs was increased as compared to non-metastatic LNs. Surprisingly, the percentage of DCregs positively correlated with the percentage of PD-1+ T cells, Tregs and CD45RO+ Tregs. Our results confirm the utility of flow cytometric analysis of EBUS/TBNA samples to assess the interaction between immune cells in TME. DCregs strongly associates with an altered T cell distribution and immunosuppressive phenotype in metastatic LNs of NSCLC patients. It can be assumed that DCregs are involved in the suppression of anti-tumor response, which could be of importance for the response upon immunotherapy.