Myeloid antigen presenting cells in lung adenocarcinoma lymph nodes assessed by endobronchial ultrasound

Abstract

Introduction: In lung cancer, the immune compartment of tumor-draining lymph nodes (TDLN) undergoes profound modifications. The immunological response is dictated by antigen presenting cells (APCs). If proper matured, APCs may prime anti-tumour specific T-cell populations. However, the role of APCs in TDLN from lung cancer patients is poorly understood. Objectives: Study myeloid APCs (mAPC) in TDLN from lung adenocarcinoma patients and compare them with lymph nodes from patients with non-malignant diseases, using minimally invasive methods. Methods: Mediastinal lymph nodes were assessed by EBUS-TBNA. Cell numbers, maturation and co-stimulatory profile were evaluated by flow cytometry and cytokine expression by PCR. The association with clinical parameters was assessed. Results: TDLN from lung adenocarcinoma patients (n=24) showed a reduced immune compartment and larger epithelial compartment when compared with control (n=17). TDLN presented higher levels of infiltrating mAPCs. A decreased expression of co-stimulatory maturation molecules with lower levels of TNF-α and IL-12, and increased levels of immunosuppressive cytokines TGF-β and IL-10 was also observed. The IL-12 expression was inversely correlated with the percentage of tumor cells infiltrated in TDLN while IL-10 was directly correlated. Patients with lower expression of IL-12 in TDLN and peripheral blood mAPCs with lower expression of CD80/86 had a worse overall survival. Conclusions: mAPCs within adenocarcinoma TDLN are immature and they are biased toward a tolerance-inducing phenotype. EBUS-TBNA allows the collection of viable specimens that may provide a better insight of the immunological parameters within TDLN.