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CD40 ‐independent natural killer‐cell help promotes dendritic cell vaccine‐induced T‐cell immunity against endogenous B‐cell lymphoma
Author(s) -
Hömberg Nadine,
Adam Christian,
Riedel Tanja,
Brenner Christoph,
Flatley Andrew,
Röcken Martin,
Mocikat Ralph
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28932
Subject(s) - cell , immunology , b cell , dendritic cell , biology , immunity , endogeny , lymphoma , cell mediated immunity , natural killer cell , immune system , antibody , cytotoxic t cell , genetics , in vitro , endocrinology
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 interferon (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/cytotoxic T lymphocyte axis may commonly have relevance for DC‐based vaccination protocols in clinical settings.