Tumor stromal cells from pediatric tumors impair NK cell function and alter NKp receptor expression

• Published in: Klinische Pädiatrie
• Main Authors: Johann, PD, Vaegler, M, Gieseke, F, Pfeiffer, M, Handgretinger, R, Müller, I
• Format: Conference Proceeding
• Language: English; German
• Published: 11.05.2009
• ISSN: 0300-8630; 1439-3824
• DOI: 10.1055/s-0029-1222647

Tumor stromal cells (TStrC) are key players in tumor growth and metastasis. Most clinical studies aim at overexpressed molecules on TStrC, however it is not fully understood how TStrC promote and orchestrate tumor growth. We established TStrC from ten pediatric tumors and compared these cultures with multipotent mesenchymal stromal cells (MSC) from bone marrow as physiological stroma. TStrC showed comparable growth behaviour as MSC. The morphological and immunological phenotype of TStrC and MSC were indistinguishable. As MSC are known to inhibit proliferation of peripheral blood mononuclear cells in vitro, we speculated that due to the similarities observed so far, TStrC may contribute to immune evasion strategies of the tumor. Interestingly, TStrC exerted a similar anti-proliferative effect on PBMC as MSC in these assays. To assess functional relevance of this inhibition we concentrated on NK cells. Histological studies underline that NK cells are in close cell-cell contact to TStrC within solid tumors. We cocultured NK cells with TStrC and examined their cytotoxic activitiy against K562. A substantial reduction in the killing of the tumor cells could be demonstrated for the cocultured NK cells. Analyzing the expression of crucial receptors involved in tumor cell lysis, we saw a downregulation of activating NK cell receptors such as NKp44 and NKp46, while the expression of other receptors such as NKG2A remained stable. NK cells are perceived as important contributors to the innate tumor defense. Thus the reduction of their cytotoxic activity by TStrC may contribute to an immune privileged area within pediatric tumors.