Langerhans cells from human cutaneous squamous cell carcinoma induce strong type 1 immunity.

Fujita H, Suárez-Fariñas M, Mitsui H, Gonzalez J, Bluth MJ, Zhang S, Felsen D, Krueger JG, Carucci JA.

Journal	J Invest Dermatol.	Year	2012
Species	Human	Volume	132 (6)
Analytes Measured	GM-CSF, IFN-γ, IL-1β, IL-10, IL-12 p70, IL-2, IL-6, IL-8, TGF-β1, TNF-α, VEGF	Page #	1645-1655
Matrix Tested	Cell culture supernatants	Category	Cytokines & Chemokines

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.