PuSH - Publication Server of Helmholtz Zentrum München

Hömberg, N. ; Adam, C. ; Riedel, T. ; Brenner, C. ; Flatley, A. ; Röcken, M.* ; Mocikat, R.

CD40-independent NK-cell help promotes dendritic cell vaccine-induced T-cell immunity against endogenous B-cell lymphoma.

Int. J. Cancer 135, 2825-2833 (2014)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
It is well established that an interplay between natural killer (NK) cells and dendritic cells (DCs) gives rise to their reciprocal activation and provides a Th1-biased cytokine milieu that fosters antitumor T-cell responses. Ex-vivo differentiated DCs transferred into mice strongly stimulate endogenous NK cells to produce IFN-γ and initiate a cascade that eventually leads to cytotoxic T-lymphocyte responses. We show that the ability of exogenous DCs to trigger this pathway obviates CD40 signaling and CD4(+) T-cell help and depends on a preceding maturation step. Importantly, this mechanism was also effective in endogenously arising tumors where IFN-γ production is compromised in contrast to transplantable tumors. In c-myc-transgenic mice developing spontaneous lymphomas, injection of unpulsed DCs caused NK-cell activation and induced CD8(+) T cells capable of recognizing the lymphoma cells. Animals treated with unpulsed DCs showed a survival benefit compared to untreated myc mice. Hence, tumor immunity induced by DC-based vaccines not only depends on specific antigens loaded on the DCs. Rather, DC vaccines generate broader immune responses, because endogenous DCs presenting tumor antigens may also become stimulated by NK cells that were activated by exogenous DCs. Thus, the DC/NK-cell/CTL axis may commonly have relevance for DC-based vaccination protocols in clinical settings.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Ctl Response ; Dc Maturation ; Adaptive Antitumor Immunity ; Interferon-γ ; λ-myc Mouse; Antitumor Immunity; Nk Cells; In-vivo; Tumor; Responses; Antigen; Recruitment; Induction; Receptor; Therapy
ISSN (print) / ISBN 0020-7136
e-ISSN 1097-0215
Journal International Journal of Cancer
Quellenangaben Volume: 135, Issue: 12, Pages: 2825-2833 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)