Mikozis Fungoides Mikroçevresinde Bulunan Dermal Fibroblastların Anti-Tümör İmmün Yanıta Etkisi

Abstract

Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. The interaction of the neoplastic lymphocytes with their microenvironment is of crucial importance in disease progression. Cancer associated fibroblasts are activated fibroblasts located in the tumor microenvironment which affect tumor growth and anti-tumor immune response. In this study, it was aimed to investigate the role of fibroblasts in the growth of MF cells and in anti-tumor immune response. In this context, fibroblasts from MF lesions and perilesional healthy skin, CD4+ T-cells from peripheral blood and neoplastic cells from MF lesions were isolated and the effects of fibroblasts on lymphocytes were investigated through co-culture experiments. It was found that fibroblasts show inhibitory effect on CD4+ T-helper cells and stimulatory effect on malignant T-cells in proliferation experiments. This effect was more prominent with normal dermal fibroblasts in both types of lymphocytes. The proliferation assays performed with MF cell lines showed comparable results with primary lymphocytes isolated from skin. The levels of interferon-gamma and interleukin-13 in co-culture supernatants were found to be higher in co-culture of CD4+ T-cells with cancer associated fibroblasts compared to that with normal fibroblasts. The opposite of this result was obtained in co-culture experiments of the cells isolated from skin. Interleukin-4 and interleukin-10 which are other Th2 cytokines were also found to be higher with cancer associated fibroblasts compared to normal fibroblasts in co-culture experiments performed with CD4+ T-cells. These results point out that normal dermal fibroblasts may have a role in MF etiopathogenesis and that fibroblasts in tumor microenvironment may exert a slowing effect on tumor growth, thus contributing to the fact that MF is a slowly progressing malignancy.