Immature myeloid cells and tolerogenic cytokines in lung adenocarcinoma metastatic lymph nodes

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Immature myeloid cells and tolerogenic cytokines in lung adenocarcinoma metastatic lymph nodes

Wednesday, 09.09.2015

Non-small-cell lung cancer (NSCLC) is one of the most common causes of cancer-related death worldwide. In this type of cancer, immunotherapy has shown inconsistent efficacy, due to our limited understanding of the molecular and cellular interactions developed during carcinogenesis.

The myeloid antigen presenting cells (mAPC) play a key role in tumor immunity, to capture, process and present tumor derived antigens to T cells, thereby allowing the initiation of the adaptive immune response. Accumulating evidence implicates the tumor-draining lymph node (TDLN) in tumor-induced immune escape, as it drains regulatory molecules and leukocytes from the tumor microenvironment. The presence of immature mAPCs infiltrated into TDLN has been reported. However, the clinical role of mAPCs infiltrated in TDLN from lung cancer patients is poorly understood.

This study published in the journal Tumor Biology allowed to highlight the importance of evaluating mAPC functions infiltrating in TDLN from lung adenocarcinoma. The mAPCs could serve as a therapeutic target for new approaches to target tumor itself and particularly to stimulate the immune response, thus improving the efficacy of current NSCLC treatments. 

 

Authors and Affiliations:

Antonio Bugalho1,2, Catarina Martins1, Zelia Silva1, Gloria Nunes1, Andreia S Mendes1, Inês Ferreira1, Paula A Videira 1,3

1 - CEDOC, Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisbon, Portugal

2 - Hospital CUF Infante Santo e Hospital CUF Descobertas, Lisbon, Portugal

3 - Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Lisbon, Portugal

 

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). TDLN from lung adenocarcinoma patients showed a reduced immune cell compartment, but a higher level of infiltrating mAPCs, when compared with control lymph node. 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. Overall, 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.

 

Journal: Tumor Biology

 

Link: http://link.springer.com/article/10.1007%2Fs13277-015-3885-1