Abstract
The safety and feasibility of dendritic cell (DC)-based immunotherapies in cancer management have been well documented after more than twenty-five years of experimentation, and, by now, undeniably accepted. On the other hand, it is equally evident that DC-based vaccination as monotherapy did not achieve the clinical benefits that were predicted in a number of promising preclinical studies. The current availability of several immune modulatory and targeting approaches opens the way to many potential therapeutic combinations. In particular, the evidence that the immune-related effects that are elicited by immunogenic cell death (ICD)-inducing therapies are strictly associated with DC engagement and activation strongly support the combination of ICD-inducing and DC-based immunotherapies. In this review, we examine the data in recent studies employing tumor cells, killed through ICD induction, in the formulation of anticancer DC-based vaccines. In addition, we discuss the opportunity to combine pharmacologic or physical therapeutic approaches that can promote ICD in vivo with in situ DC vaccination.
Highlights
Dendritic cells (DCs) represent the sentinels of the immune system and they play an important role in linking innate and adaptive immune responses [1]
Several clinical studies have pointed to the limitations of DC-based protocols despite the ability of DC-based vaccines to elicit measurable immunological responses, whereby this approach fails to generate effective and lasting clinical antitumor responses, especially when used as monotherapy [181]
Several preclinical studies employing immunogenic cell death (ICD)-DC-based vaccines indicated that an ICD-derived cargo could boost the stimulation of tumor-specific cytotoxic T lymphocyte (CTL) to achieve efficient tumor control
Summary
Dendritic cells (DCs) represent the sentinels of the immune system and they play an important role in linking innate and adaptive immune responses [1]. In the last two decades, several studies have shown that some anticancer agents, including chemotherapeutics and physical therapeutic modalities, can exert immunomodulatory activities, which directly affect immune cells in the TME, including DCs, or, indirectly, modifying the cancer cell immunogenicity by the induction of immunogenic cell death (ICD) [13,14,15] Most of these anticancer treatments promote ICD through reactive oxygen species (ROS) generation and Endoplasmic Reticulum (ER) stress [16,17,18], causing the release or the surface exposure of a series of DAMPs through a well-defined spatiotemporal scheme [19]. The present review investigates and discusses the opportunity to combine the potentiality of DC-based immunotherapy with the peculiar anticancer activity of ICD inducers
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