Abstract
T cell lymphomas arise in mice that constitutively express a single TCR in the absence of NK cells. Upon TCR engagement these lymphomas are able to corrupt tumor surveillance by decreasing NK cell numbers. In this study, we investigate the outcome of interactions between these T cell lymphomas and dendritic cells. Bone marrow–derived dendritic cells mediated effective killing of T cell lymphomas after activation with IFN-γ and TLR ligands in culture. This cytotoxicity was independent of MHC compatibility. Cell lysis was reduced by the presence of the peroxynitrite inhibitors FeTTPS and L-NMMA, whereas inhibitors of apoptosis, death receptors, and degranulation were without effect, suggesting NO metabolites as the main mediators. When injected together with GM-CSF and R848 into lymphoma-bearing mice, in vitro–expanded bone marrow–derived dendritic cells caused significant survival increases. These data show that dendritic cell adaptive immunotherapy can be used as treatment against T cell lymphomas in mice.
Highlights
Why The JI? Submit online. Rapid Reviews! 30 days* from submission to initial decision No Triage! Every submission reviewed by practicing scientists Fast Publication! 4 weeks from acceptance to publicatio
dendritic cells (DCs) appear to play an important role in the life of T cell lymphomas [7, 8, 16]
An involvement of Agpresenting DCs in the survival and progression of T cell lymphomas is suggested by the relative intactness of TCR signaling cascades in these tumors as well as by the existence of mutations that constitutively activate TCR pathways [7, 8]
Summary
Bone marrowderived dendritic cells mediated effective killing of T cell lymphomas after activation with IFN-g and TLR ligands in culture. When injected together with GM-CSF and R848 into lymphoma-bearing mice, in vitroexpanded bone marrowderived dendritic cells caused significant survival increases. Our data show a direct cytotoxic response of DCs against T cell lymphomas in vitro and in vivo.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
