Melanoma, despite its aggressive growth characteristics, is an antigenic tumor expressing several characterized neo‐ and differentiation antigens. Dendritic cells (DC) when pulsed with definedpeptides have been shown to effectively induce melanoma‐specific T cell responses in humans and mice. These protect animals from challenge with melanoma, but so far have failed to induce significant tumor regressions. To study the efficacy of DC‐based anti‐tumor vaccinations, we set up a therapeutic model using C57BL/6J mice with established pulmonary and subcutaneous metastases induced by the B16‐melanoma cell line B78‐D14. Mice were vaccinated twice with 20,000 antigen‐presenting cells, either bone marrow‐derived DC or epidermal Langerhans cells (LC), which were loaded with the tyrosinase‐related protein 2 (TRP2) peptide. Generally, DC cultured with fetal calf serum (FCS) induced a dominant unspecific response. This was not seen using LC cultured without serum; however, vaccination with TRP2‐loaded FCS‐free LC alone failed to influence the growth of established B16 tumors. A reproducible reduction of tumor size and weight was only obtained if LC vaccinations with TRP2 were followedby a 5‐day treatment of mice with 200,000 IU IL‐2 intraperitoneally twice/daily. Omitting the TRP2 peptide abolished the efficacy of this combined treatment, demonstrating the crucial role of priming a melanoma‐specific T cell response. Microcytotoxic assays performed with spleen‐derived T cells and melanoma as well as congenic fibroblast lines as targets confirmed the TRP2‐dependent specificity of LC‐induced immune responses. Thus, despite the fact that tumor‐specific T cells were primed, an additional IL‐2‐dependent stimulus was needed to translate this immune response into a therapeutic effect against established tumors.

The expression of Fas ligand has recently been proposed as a novel tumor escape mechanism for melanoma. To establish the characteristics of Fas ligand expression during the course of melanoma progression we performed a longitudinal study analyzing primary tumors as well as subsequently evolving metastases. In primary melanoma Fas ligand was expressed in two of 20 lesions; this expression was weak and restricted to few parts of the tumors. The Fas ligand positive primary melanomas were rather thick, i.e., 8.5 and 3.8 mm, versus a median of 2.4 mm of the remaining tumors. In contrast, for metastatic melanoma Fas ligand expression was present in six of 11 cases investigated. The metastases of primary tumors displaying Fas ligand maintained its expression. As Fas ligand positive melanoma cells are capable of inducing apoptosis in susceptible cells, e.g., Fas positive tumor infiltrating lymphocytes, we tested for the presence of apoptotic cells in situ by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. This analysis revealed that apoptotic cells were present within the Fas ligand positive tumors. The number of apoptotic cells, however, never exceeded 5% of the total cells. Thus, Fas ligand mediated apoptosis does not seem to be a major immune escape mechanism for melanoma but its expression correlates with the stage of melanoma.

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Like many other animals, mammals develop from fertilized oocytes – the ultimate stem cells. As embryogenesis proceeds, most cells lose developmental potential and eventually become restricted to a specific cell lineage. The result is the formation of a complete and structured mature organism with complex organs composed of a great variety of mature, mostly mitotically quiescent effector cells. However, along the way, some exceptional cells, known as somatic stem cells (SSCs) are set aside and maintain a high proliferation and tissue-specific differentiation potential. SSCs, in contrast to embryonic stem (ES) cells, which are able to give rise to all cell types of the body, have been regarded as being more limited in their differentiation potential in the sense that they were thought to be committed exclusively to their tissue of origin. However, recent studies have demonstrated that somatic stem cells from a given tissue can also contribute to heterologous tissues and thus show a broad nontissue restricted differentiation potential. The question arises: how plastic are somatic stem cells? To provide a tentative answer, we describe and review here recent investigations into the developmental potentials of two somatic stem cell types, namely hematopoietic and neural stem cells.