Myeloid dendritic cells from human cutaneous squamous cell carcinoma are poor stimulators of T-cell proliferation.
To determine the phenotype and function of myeloid dendritic cells (DCs) from human cutaneous squamous-cell carcinoma (SCC), we studied their surface marker expression and allo-stimulatory potential ex vivo. There were abundant CD11c(+) myeloid DCs, as well as TNF and inducible nitric oxide synthase (iNOS)-producing DCs, in and around SCC tumor nests. Although myeloid DCs from SCC, adjacent non-tumor-bearing skin, and normal skin, were phenotypically similar by flow cytometry, and there was a pronounced genomic signature of mature DCs in SCC, they showed different T-cell stimulatory potential in an allogeneic mixed leukocyte reaction. Myeloid DCs from SCC were less potent stimulators of allogeneic T-cell proliferation than DCs from non-tumor-bearing skin. Culture with a DC-maturing cytokine cocktail (IL-1beta, IL-6, TNF-alpha, and PGE(2)) enhanced stimulatory potential in DCs from non-tumor-bearing skin, whereas SCC-associated DCs remained poor stimulators of T-cell proliferation. The microenvironment associated with SCC showed expression of TGF-beta, IL-10, and VEGF-A, factors capable of suppressing the DC function. These findings indicate that CD11c(+)/HLA-DR(hi) DCs from SCC are mature, but are not potent stimulators of T-cell proliferation compared with phenotypically similar DCs isolated from non-tumor-bearing skin. Identification of mechanisms responsible for suppression of tumor-associated DCs may provide insight into the evasion of immunosurveillance by SCC.
Bluth
Mark J
MJ
Department of Dermatology, Weill Medical College of Cornell University, New York, New York 10021, USA.
Zaba
Lisa C
LC
Moussai
Dariush
D
Suárez-Fariñas
Mayte
M
Kaporis
Helen
H
Fan
Linda
L
Pierson
Katherine C
KC
White
Traci R
TR
Pitts-Kiefer
Alexander
A
Fuentes-Duculan
Judilyn
J
Guttman-Yassky
Emma
E
Krueger
James G
JG
Lowes
Michelle A
MA
Carucci
John A
JA
D018949:Antigens, CD1 / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007801:Langerhans Cells / Q000378:metabolism / Q000473:pathology; D037181:Lectins, C-Type / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D018307:Neoplasms, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018949:Antigens, CD1; C419393:CD1a antigen; C443299:CLEC4C protein, human; D006684:HLA-DR Antigens; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II