CD95 ligand expression mediates immune escape in breast cancer
© BioMed Central Ltd 2001
Received: 10 May 2001
Published: 31 May 2001
Interaction of CD95 and its ligand (CD95L) plays an important role in the regulation of immune response, since CD95 + lymphocytes may be killed after engagement of the CD95 receptor. Studying the CD95/CD95L system in 40 cases of breast cancer, the malignant cells expressed CD95L, but lost CD95 expression, when compared to non-malignant mammary epithelia. In addition, four breast cancer lines expressed CD95L, which was further enhanced, when the cells were treated with IFN-γ. This was functionally relevant, because Jurkat T cells incubated on breast cancer cells underwent CD95L specific apoptosis and the rate of apoptosis was demonstrated by inhibition of matrix metalloproteinases, CD95L expressed on breast cancer cells could also be shed from the cell membrane into the culture supernatant and supernatants derived from breast cancer cell cultures induced CD95L specific apoptosis in Jurkat T cells. Interestingly, in breast cancer patients depletion of CD4 + and CD8 + peripheral blood lymphocytes was tightly correlated with CD95 ligand expression in the tumours, which is suggestive for a relationship between CD95 ligand expression by tumour and systemic immunosuppression.