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

J Invest Dermatol. 2012 Jun;132(6):1645-55. doi: 10.1038/jid.2012.34. Epub 2012 Mar 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / therapy
  • Cell Communication / immunology
  • Cell Division / immunology
  • Cell Polarity / immunology
  • Gene Expression Profiling
  • Humans
  • Immune Tolerance / genetics
  • Immune Tolerance / immunology
  • Immunotherapy, Adoptive / methods*
  • Interferon-gamma / metabolism
  • Langerhans Cells / cytology*
  • Langerhans Cells / immunology*
  • Monocytes / cytology
  • Skin Neoplasms / genetics
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / therapy

Substances

  • Interferon-gamma