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Updated: Aug 8, 2026
Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
Tumor antigen presentation by murine epidermal cells
S Grabbe1, S Bruvers, R L Gallo
1Wellman Laboratories of Photomedicine, Harvard Medical School, Boston, MA 02114.
Insights
Murine epidermal cells (EC) pulsed with tumor fragments can induce antitumor immunity. This process requires granulocyte-macrophage-colony-stimulating factor culture and I-A+ cells for effective tumor antigen presentation.
Area of Science:
- Immunology
- Dermatology
- Oncology
Background:
- Epidermal Langerhans cells present antigens (Ag) for CD4-dependent immunity.
- Langerhans cells are hypothesized to present tumor-associated Ag in situ for antitumor immunity.
Purpose of the Study:
- To investigate the capacity of murine epidermal cells (EC) to present tumor-associated Ag for inducing in vivo antitumor immunity.
Main Methods:
- Murine EC were depleted of Thy-1+ cells and cultured with granulocyte-macrophage-colony-stimulating factor (GM-CSF).
- EC were pulsed with tumor fragments (TF) from S1509a-fibrosarcoma and injected into syngeneic recipients.
- Immunity was assessed by tumor challenge and delayed-type hypersensitivity (DTH) response. I-A+ cells were depleted using antibody and complement lysis.
Main Results:
- TF-pulsed EC induced protective immunity against tumor growth in vivo.
- TF-pulsed EC also induced a significant DTH response to tumor cells.
- Immunity induction was genetically restricted and required GM-CSF culture.
- Deletion of I-A+ cells abolished the generation of antitumor immunity.
Conclusions:
- I-A+ epidermal cells are capable of presenting S1509a tumor Ag.
- This presentation generates protective antitumor immunity in vivo.
- GM-CSF culture is essential for the development of this immunity.
Abstract:
The ability of epidermal Langerhans cells to present Ag for CD4-dependent immunity is well documented, and it has been hypothesized that Langerhans cells participate in the generation of immunity against incipient epidermal neoplasms by presentation of tumor-associated Ag in situ. This study examined the ability of murine epidermal cells (EC) to present tumor-associated Ag for the induction of in vivo antitumor immunity. Murine epidermal cells were deleted of Thy-1-bearing cells, cultured in 50 U/ml granulocyte-macrophage-CSF for 14 to 18 h, and pulsed with tumor fragments (TF) derived from S1509a-fibrosarcoma cells. These TF-pulsed EC were injected s.c. into syngeneic recipients at weekly intervals for a total of three immunizations and challenged with viable S1509a tumor cells 1 wk after the last immunization. Control animals received TF-pulsed allogeneic EC or EC treated identically but not pulsed with TF. EC that were pulsed with tumor cell fragments were able to induce protective immunity to tumor growth in vivo and to immunize for a significant delayed-type hypersensitivity response to injected tumor cells. The induction of antitumor immunity with TF-pulsed EC was genetically restricted, and culture of EC in granulocyte-macrophage-CSF was required for development of significant immunity. Furthermore, deletion of I-A+ cells by antibody and complement-mediated lysis eliminated the generation of immunity. Thus, I-A+ epidermal cells are capable of presenting S1509a tumor Ag for the generation of protective antitumor immunity in vivo.
