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Tumor Biology

, Volume 37, Issue 1, pp 953–961 | Cite as

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

  • Antonio Bugalho
  • Catarina Martins
  • Zelia Silva
  • Gloria Nunes
  • Andreia S Mendes
  • Inês Ferreira
  • Paula A Videira
Original Article

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.

Keywords

Antigen-presenting cells Lymph node Non-small cell lung cancer Endobronchial ultrasound Adenocarcinoma Metastasis 

Notes

Acknowledgments

We thank Manuela Correia for the technical assistance.

Conflicts of interest

None

Funding sources

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Antonio Bugalho
    • 1
    • 2
  • Catarina Martins
    • 1
  • Zelia Silva
    • 1
  • Gloria Nunes
    • 1
  • Andreia S Mendes
    • 1
  • Inês Ferreira
    • 1
  • Paula A Videira
    • 1
    • 3
  1. 1.CEDOC, Chronic Diseases Research Center, NOVA Medical School/Faculdade de Ciências MédicasUniversidade Nova de LisboaLisbonPortugal
  2. 2.Hospital CUF Infante Santo e Hospital CUF DescobertasLisbonPortugal
  3. 3.Departamento Ciências da Vida, Faculdade de Ciências e TecnologiaUniversidade Nova de LisboaLisbonPortugal

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