Cancer Immunology, Immunotherapy

, Volume 55, Issue 5, pp 598–611

Lung squamous cell carcinoma and adenocarcinoma cell lines use different mediators to induce comparable phenotypic and functional changes in human monocyte-derived dendritic cells

  • Federico Àvila-Moreno
  • José Sullivan López-González
  • Griselda Galindo-Rodríguez
  • Heriberto Prado-García
  • Sandra Bajaña
  • Carmen Sánchez-Torres
Original Article

DOI: 10.1007/s00262-005-0060-3

Cite this article as:
Àvila-Moreno, F., López-González, J.S., Galindo-Rodríguez, G. et al. Cancer Immunol Immunother (2006) 55: 598. doi:10.1007/s00262-005-0060-3

Abstract

Tumor-derived immunosuppressive factors contribute to the evasion of malignant cells from the immune response, partially by hampering dendritic cell (DC) differentiation. Here, we analyze whether soluble mediators released by the most frequent histological types of non-small cell lung carcinoma, squamous cell carcinoma (SCC), and adenocarcinoma (AD) cells, affect the development and functionality of DC. Monocytes from healthy donors were differentiated in vitro into DC with granulocyte–macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4, in the absence or presence of soluble factors (SF) from SCC or AD cell lines. Monocytes were differentiated in parallel into macrophages (MΦ s) with macrophage colony-stimulating factor (M-CSF). SF-treated DC were phenotypically and functionally more similar to MΦ s than to untreated DC [control DC (Ctrl-DC)]. Both tumors increased myelomonocytic markers (CD14, CD16, CD32, and CD163) and impaired CD1a expression on DC. SF-treated DC increased their endocytic capacity, and released higher levels of IL-6, IL-10, and lower levels of IL-12, compared to Ctrl-DC. SF-treated DC were poor stimulators in mixed lymphocyte reactions, and naïve CD4+ T lymphocytes stimulated by SF-treated DC secreted lower levels of interferon (IFN)-γ and higher amounts of IL-10 than controls. In contrast to AD, the effects caused by SCC were mostly abolished by IL-6 neutralization during monocyte differentiation. However, tumor-derived prostanoid blockade recovered the IFN-γ levels secreted by lymphocytes stimulated with SF-treated DC, whereas prostanoid/IL-6 or prostanoid/IL-10 blockade decreased IL-10 production only by SCC-DC-stimulated lymphocytes. Thus, we provide evidence that lung SCC and AD cause comparable deficiencies on DC in vitro, skewing monocyte differentiation from DC to MΦ -like cells, but most of these changes occurred via different mediators.

Keywords

Lung carcinoma Dendritic cell differentiation Interleukin-6 

Abbreviations

AD

Adenocarcinoma

APC

Antigen presenting cell

CM

Conditioned media

COX

cyclooxygenase

Ctrl-DC

Control DC

DC

Dendritic cell

GM-CSF

Granulocyte–macrophage colony-stimulating factor

IFN

Interferon

IL

Interleukin

LPS

Lipopolysaccharide

mAb

Monoclonal antibody

M-CSF

Macrophage colony-stimulating factor

Macrophage

NSCLC

Non-small cell lung carcinoma

PBMC

Peripheral blood mononuclear cells

PG

Prostaglandin

SCC

Squamous cell carcinoma

SF

Soluble factors

TGF

Transforming growth factor

TNF

Tumor necrosis factor

TT

Tetanus toxoid

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Federico Àvila-Moreno
    • 1
    • 2
  • José Sullivan López-González
    • 2
  • Griselda Galindo-Rodríguez
    • 1
    • 3
  • Heriberto Prado-García
    • 2
  • Sandra Bajaña
    • 4
  • Carmen Sánchez-Torres
    • 1
  1. 1.Department of Molecular BiomedicineCentro de Investigación y de Estudios Avanzados-IPN (CINVESTAV-IPN)Mexico CityMexico
  2. 2.Departamento de Enfermedades Crónico-DegenerativasInstituto Nacional de Enfermedades Respiratorias (INER)Mexico CityMexico
  3. 3.Rheumatic Disease Unit, Hospital de Especialidades Centro Medico Nacional La RazaInstituto Mexicano del Seguro SocialMexico CityMexico
  4. 4.Sección de Estudios de Posgrado e InvestigaciónEscuela Superior de Medicina del IPNMexico CityMexico