CD95L mediates tumor counterattack in vitro but induces neutrophil‐independent tumor rejection in vivo

• DOI: 10.1002/ijc.20538
• Publication Date: 2004-08-25T17:06:01Z
• Authors: Frederik H. Igney; Christian K. Behrens; Peter H. Krammer
• Keywords: Cytotoxicity, Immunologic; Mice, Knockout; Mice, Inbred BALB C; Fas Ligand Protein; Membrane Glycoproteins; Neutrophils; Reverse Transcriptase Polymerase Chain Reaction; Mice, Nude; NADPH Oxidases; Nitric Oxide Synthase Type II; Neoplasms, Experimental; CD8-Positive T-Lymphocytes; Phosphoproteins; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; 0302 clinical medicine; Animals; Female; fas Receptor; Nitric Oxide Synthase; T-Lymphocytes, Cytotoxic

AbstractMany tumors express CD95L (CD178, FasL, APO‐1L) and may thus kill tumor‐infiltrating lymphocytes, a phenomenon called tumor counterattack. However, presently it is not clear whether tumor counterattack is a relevant immune escape mechanism. To characterize the effect of CD95L expression of tumor cells on tumor‐specific T cells, we established an in vitro system with TCR tg T cells and a model tumor antigen. Preactivated antitumor T cells were able to kill CD95L− and CD95L+ tumor cells. CD95L+ tumor cells killed activated T cells in vitro and inhibited the expansion of cytotoxic antitumor T cells in mixed lymphocyte tumor reactions. In vivo CD95L expression led to delayed tumor growth or complete tumor rejection. Neutrophils were not responsible for the delayed growth of the CD95L+ tumors tested. In mice with neutrophils deficient for important cytotoxicity mechanisms (p47phox−/− or iNOS−/− mice), CD95L+ tumors grew similarly as in wild‐type mice. Incidence and growth rate of CD95L+ tumors in mice injected with a neutrophil‐depleting or an isotype control antibody was the same. In CD95‐deficient lpr mice, tumor growth was not altered as compared to wild‐type mice. Taken together, CD95L mediated tumor counterattack in vitro, but led to neutrophil‐independent tumor rejection in vivo.