title: Langerhans cells from human cutaneous squamous cell carcinoma induce strong type 1 immunity.
abstract: Langerhans cells (LCs) are dendritic cells (DCs) localized to the epidermis. They should be the first antigen-presenting cells to encounter squamous cell carcinoma (SCC). The aim of this study was to investigate the ability of LCs isolated from human SCC to induce T-cell proliferation and polarization. We investigated the ability of LCs from SCC and peritumoral skin to induce T-cell proliferation and polarization. We also studied the effect of SCC supernatant on the ability of LCs from normal skin, in vitro-generated LCs, and DCs to activate and polarize T cells. LCs from SCC were stronger inducers of allogeneic CD4(+) and CD8(+) T-cell proliferation and IFN-γ production than LCs from peritumoral skin. We found that tumor supernatants (TSNs) were rich in immunosuppressive cytokines; despite this, allogeneic CD4(+) and CD8(+) T-cell proliferation and IFN-γ induction by LCs were augmented by TSN. Moreover, TSN facilitated IFN-γ induction by in vitro-generated LCs, but suppressed the ability of in vitro-generated DCs to expand allogeneic CD4(+) and CD8(+) T cells. We have demonstrated that LCs from SCC can induce type 1 immunity. TSN induces IFN-γ induction by in vitro-generated LCs. This contrasts greatly with prior studies showing that DCs from SCC cannot stimulate T cells. These data indicate that LCs may be superior to DCs for SCC immunotherapy and may provide a new rationale for harnessing LCs for the treatment of cancer patients.
authors.affiliation: Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York , USA.
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujita
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsui
authors.forename: Juana
authors.initials: J
authors.lastname: Gonzalez
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Bluth
authors.forename: Shali
authors.initials: S
authors.lastname: Zhang
authors.forename: Diane
authors.initials: D
authors.lastname: Felsen
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.forename: John A
authors.initials: JA
authors.lastname: Carucci
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D002450:Cell Communication / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D007801:Langerhans Cells / Q000166:cytology* / Q000276:immunology*; D009000:Monocytes / Q000166:cytology; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy
chemical_list: D007371:Interferon-gamma