A Novel Dendritic Cell-Based Vaccination Protocol to Stimulate Immunosurveillance of Aggressive Cancers

Nigro, Annunziata; Montico, Barbara; Casolaro, Vincenzo; Col, Jessica Dal

doi:10.1007/978-1-4939-8885-3_22

Cited by 9 publications

(6 citation statements)

References 27 publications

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“…In recent years, anticancer vaccination success has been correlated with the immunogenic potential of dead/dying cells used as antigen/adjuvant source. The danger signals-dependent efficacy of ICD-based DC vaccines has recently been shown (17, 51–54). However, chemical ICD inducers are not desirable for production of DC-based vaccines because they either leave residual drug concentrations behind or may exert cytotoxicity against DCs.…”

Section: Discussionmentioning

confidence: 99%

Photodynamic Modulation of Type 1 Interferon Pathway on Melanoma Cells Promotes Dendritic Cell Activation

et al. 2019

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The immune response against cancer generated by type-I-interferons (IFN-1) has recently been described. Exogenous and endogenous IFN-α/β have an important role in immune surveillance and control of tumor development. In addition, IFN-1s have recently emerged as novel DAMPs for the consecutive events connecting innate and adaptive immunity, and they also have been postulated as an essential requirement for induction of immunogenic cell death (ICD). In this context, photodynamic therapy (PDT) has been previously linked to the ICD. PDT consists in the administration of a photosensitizer (PS) and its activation by irradiation of the affected area with visible light producing excitation of the PS. This leads to the local generation of harmful reactive oxygen species (ROS) with limited or no systemic defects. In the current work, Me-ALA inducing PpIX (endogenous PS) was administrated to B16-OVA melanoma cells. PpIX preferentially localized in the endoplasmic reticulum (ER). Subsequent PpIX activation with visible light significantly induced oxidative ER-stress mediated-apoptotic cell death. Under these conditions, the present study was the first to report the in vitro upregulation of IFN-1 expression in response to photodynamic treatment in melanoma. This IFN-α/β transcripts upregulation was concurrent with IRF-3 phosphorylation at levels that efficiently activated STAT1 and increased ligand receptor (cGAS) and ISG (CXCL10, MX1, ISG15) expression. The IFN-1 pathway has been identified as a critical molecular pathway for the antitumor host immune response, more specifically for the dendritic cells (DCs) functions. In this sense, PDT-treated melanoma cells induced IFN-1-dependent phenotypic maturation of monocyte-derived dendritic cells (DCs) by enhancing co-stimulatory signals (CD80, MHC-II) and tumor-directed chemotaxis. Collectively, our findings showed a new effect of PDT-treated cancer cells by modulating the IFN-1 pathway and its impact on the activation of DCs, emphasizing the potential relevance of PDT in adoptive immunotherapy protocols.

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Section: Discussionmentioning

confidence: 99%

Photodynamic Modulation of Type 1 Interferon Pathway on Melanoma Cells Promotes Dendritic Cell Activation

et al. 2019

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“…We have recently proposed the use of a 9-cis-retinoic acid (RA)/IFN-α combination as a novel and highly effective modality to induce ICD ex vivo in aggressive and/or refractory lymphoma cells for the optimization of DC-based vaccines [121,122]. The RA/IFN-α combination stimulated autophagy [123] and induced high levels of apoptosis in vitro [124], and highly immunogenic tumor cell lysates that were generated following this treatment were successfully used for DC loading (100 µg of tumor lysate for 10 6 DCs).…”

Section: Ifn-αmentioning

confidence: 99%

Dendritic Cells and Immunogenic Cancer Cell Death: A Combination for Improving Antitumor Immunity

et al. 2020

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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.

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“…Based on these considerations, we proposed here to define miRNAs expression pattern of cancer cells undergoing ICD and to identify the potential contribution of these small non-coding sequences to cancer cell immunogenicity. To this end, we adopted our previously described model of immunogenic apoptosis in which ICD is induced in lymphoma cell lines by the combination of retinoic acid (RA) and interferon-α (IFN-α) [ 18 , 19 , 20 ]. We have demonstrated that the RA/IFN-α combination induced immunogenic apoptosis characterized by expression of ICD hallmarks.…”

Section: Introductionmentioning

confidence: 99%

“…Consistently, RA/IFN-α-treated apoptotic cells were preferentially recognized and engulfed in vitro by monocyte-derived dendritic cells (DCs) compared to controls. In addition, previous results indicated that DCs loaded with immunogenic tumor cell lysates obtained from RA/IFN-α-treated lymphoma cell lines were highly efficient in eliciting tumor and antigen-specific cytotoxic T lymphocytes in vitro and in mediating tumor growth inhibition in vivo [ 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Integration of miRNA:mRNA Co-Expression Revealed Crucial Mechanisms Modulated in Immunogenic Cancer Cell Death

Lamberti

Montico

Ravo³

et al. 2022

Biomedicines

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Immunogenic cell death (ICD) in cancer represents a functionally unique therapeutic response that can induce tumor-targeting immune responses. ICD is characterized by the exposure and release of numerous damage-associated molecular patterns (DAMPs), which confer adjuvanticity to dying cancer cells. The spatiotemporally defined emission of DAMPs during ICD has been well described, whereas the epigenetic mechanisms that regulate ICD hallmarks have not yet been deeply elucidated. Here, we aimed to examine the involvement of miRNAs and their putative targets using well-established in vitro models of ICD. To this end, B cell lymphoma (Mino) and breast cancer (MDA-MB-231) cell lines were exposed to two different ICD inducers, the combination of retinoic acid (RA) and interferon-alpha (IFN-α) and doxorubicin, and to non ICD inducers such as gamma irradiation. Then, miRNA and mRNA profiles were studied by next generation sequencing. Co-expression analysis identified 16 miRNAs differentially modulated in cells undergoing ICD. Integrated miRNA-mRNA functional analysis revealed candidate miRNAs, mRNAs, and modulated pathways associated with Immune System Process (GO Term). Specifically, ICD induced a distinctive transcriptional signature hallmarked by regulation of antigen presentation, a crucial step for proper activation of immune system antitumor response. Interestingly, the major histocompatibility complex class I (MHC-I) pathway was upregulated whereas class II (MHC-II) was downregulated. Analysis of MHC-II associated transcripts and HLA-DR surface expression confirmed inhibition of this pathway by ICD on lymphoma cells. miR-4284 and miR-212-3p were the strongest miRNAs upregulated by ICD associated with this event and miR-212-3p overexpression was able to downregulate surface expression of HLA-DR. It is well known that MHC-II expression on tumor cells facilitates the recruitment of CD4+ T cells. However, the interaction between tumor MHC-II and inhibitory coreceptors on tumor-associated lymphocytes could provide an immunosuppressive signal that directly represses effector cytotoxic activity. In this context, MHC-II downregulation by ICD could enhance antitumor immunity. Overall, we found that the miRNA profile was significantly altered during ICD. Several miRNAs are predicted to be involved in the regulation of MHC-I and II pathways, whose implication in ICD is demonstrated herein for the first time, which could eventually modulate tumor recognition and attack by the immune system.

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A Novel Dendritic Cell-Based Vaccination Protocol to Stimulate Immunosurveillance of Aggressive Cancers

Cited by 9 publications

References 27 publications

Photodynamic Modulation of Type 1 Interferon Pathway on Melanoma Cells Promotes Dendritic Cell Activation

Photodynamic Modulation of Type 1 Interferon Pathway on Melanoma Cells Promotes Dendritic Cell Activation

Dendritic Cells and Immunogenic Cancer Cell Death: A Combination for Improving Antitumor Immunity

Integration of miRNA:mRNA Co-Expression Revealed Crucial Mechanisms Modulated in Immunogenic Cancer Cell Death

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