High frequency of immature dendritic cells and altered in situ production of interleukin-4 and tumor necrosis factor-alpha in lung cancer.
BACKGROUND
Antigen-presenting cells, like dendritic cells (DCs) and macrophages, play a significant role in the induction of an immune response and an imbalance in the proportion of macrophages, immature and mature DCs within the tumor could affect significantly the immune response to cancer. DCs and macrophages can differentiate from monocytes, depending on the milieu, where cytokines, like interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) induce DC differentiation and tumor necrosis factor (TNF)-alpha induce DC maturation. Thus, the aim of this work was to analyze by immunohistochemistry the presence of DCs (S100+ or CD1a+), macrophages (CD68+), IL-4 and TNF-alpha within the microenvironment of primary lung carcinomas.


RESULTS
Higher frequencies of both immature DCs and macrophages were detected in the tumor-affected lung, when compared to the non-affected lung. Also, TNF-alpha-positive cells were more frequent, while IL-4-positive cells were less frequent in neoplastic tissues. This decreased frequency of mature DCs within the tumor was further confirmed by the lower frequency of CD14-CD80+ cells in cell suspensions obtained from the same lung tissues analyzed by flow cytometry.


CONCLUSIONS
These data are discussed and interpreted as the result of an environment that does not oppose monocyte differentiation into DCs, but that could impair DC maturation, thus affecting the induction of effective immune responses against the tumor.
Baleeiro
R B
RB
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1730, Cidade Universitária, São Paulo, SP 05508-000, Brazil.
Anselmo
L B
LB
Soares
F A
FA
Pinto
C A L
CA
Ramos
O
O
Gross
J L
JL
Haddad
F
F
Younes
R N
RN
Tomiyoshi
M Y
MY
Bergami-Santos
P C
PC
Barbuto
J A M
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018122:B7-1 Antigen / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018122:B7-1 Antigen; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor