TY - JOUR
T1 - Myeloid dendritic cells from human cutaneous squamous cell carcinoma are poor stimulators of T-cell proliferation
AU - Bluth, Mark J.
AU - Zaba, Lisa C.
AU - Moussai, Dariush
AU - Suárez-Farĩas, Mayte
AU - Kaporis, Helen
AU - Fan, Linda
AU - Pierson, Katherine C.
AU - White, Traci R.
AU - Pitts-Kiefer, Alexander
AU - Fuentes-Duculan, Judilyn
AU - Guttman-Yassky, Emma
AU - Krueger, James G.
AU - Lowes, Michelle A.
AU - Carucci, John A.
N1 - Funding Information:
Research was supported by the Dana Foundation (Human Immunology Consortium Grant), which supports JAC, DM, KCP, LF, and AP-K. MJB is supported by the National Institutes of Health (NIH) grant T32-HL07423, LCZ is supported by NIH MSTP grant GM07739, MAL is supported by NIH grant 1 K23 AR052404-01A1, and MS-F is partially supported by NIH grant UL1 RR024143 from the National Center for Research Resources (NCRR). We thank plastic surgeons Drs AN LaBruna and DM Senderoff for their generous donation of abdominoplasty surgical waste. We also appreciate the assistance and advice of the Flow Cytometry Core Facility (Dr S Mazel, Dr X Fan, and C Bare) and the Bio-imaging Resource Center (Dr A North) at the Rockefeller University.
PY - 2009/10
Y1 - 2009/10
N2 - 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-1Β, IL-6, TNF-α, 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-Β, 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.
AB - 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-1Β, IL-6, TNF-α, 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-Β, 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.
UR - http://www.scopus.com/inward/record.url?scp=70349087826&partnerID=8YFLogxK
U2 - 10.1038/jid.2009.96
DO - 10.1038/jid.2009.96
M3 - Article
C2 - 19387481
AN - SCOPUS:70349087826
SN - 0022-202X
VL - 129
SP - 2451
EP - 2462
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 10
ER -