Immature myeloid cells and tolerogenic cytokine profile in lung adenocarcinoma metastatic lymph nodes assessed by endobronchial ultrasound

Abstract

In lung cancer, the immune cell compartment of tumor-draining lymph nodes (TDLNs) dictate the response against tumors. This response is predominantly triggered by myeloid antigen-presenting cells (mAPCs) that capture antigens and, if matured, prime anti-tumor-specific T cell populations. However, the clinical role of mAPCs infiltrated in TDLN from lung cancer patients is poorly understood. The purpose of this study was to study mAPCs in TDLN from lung adenocarcinoma patients, in comparison to individuals with non-malignant diseases, using minimally invasive sampling methods. Mediastinal lymph nodes were assessed by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). mAPCs were characterized by flow cytometry and cytokine expression by quantitative polymerase chain reaction. The association with tumor burden, overall survival, and response to treatment was assessed. TDLN from lung adenocarcinoma patients (n = 24) showed a reduced immune cell compartment, but a higher level of infiltrating mAPCs, when compared with control lymph nodes (n = 17). A decreased expression of co-stimulatory molecules CD80/CD86 by TDLN and blood mAPC was observed. TDLN showed lower levels of TNF-α and IL-12 and increased levels of immunosuppressive cytokines TGF-β and IL-10. The IL-12 expression was inversely correlated with the percentage of infiltrated tumor cells, while IL-10 was directly correlated. Patients with lower expression of IL-12 in TDLN or lower expression of CD80/86 in blood mAPCs had worse overall survival and response to therapy. mAPCs of lung adenocarcinoma patients express less co-stimulatory molecules, and within TDLN, the cytokine profile is biased towards a tolerance-inducing phenotype. Patients with enhanced immune parameters have better survival and response to treatment. EBUS-TBNA allows the collection of viable specimens from TDLN that may provide further insight on relevant immunological mechanisms.

Immunohistochemical Detection of Pro-Inflammatory and Anti-Inflammatory Interleukins in the Lungs of Sheep with Jaagsiekte

“…IL-12, which is an important regulator of the immune response, has various anti-tumoral effects (Airoldi et al, 2009;D'Amico et al, 2012). IL-12 is a useful predictive and prognostic marker for patients with lung adenocarcinoma (Bugalho et al, 2016). Larruskain et al (2012) found that the IL-12 microsatellite was the least polymorphic with 7 alleles in OPA.…”

Radiation Therapy and the In Situ Vaccination Approach

“…On the other hand, clinically and/or pathologically involved lymph nodes can be tolerogenic and thus promote local and systemic immune suppression. 74,75 The robust overall survival benefit reported in PACIFIC (NCT02125461) with the addition of durvalumab was preceded by comprehensive concurrent chemoradiation targeting the primary tumor and locoregional nodal metastases. 76 Thus, reduction in tumor burden and relief of immune suppression afforded by concurrent chemoradiation may also augment immunogenicity.…”