Generation of dendritic cell-based vaccine using high hydrostatic pressure for non-small cell lung cancer immunotherapy

Hradilova, Nada; Sadílková, Lenka; Palata, Ondřej; Myšíková, D.; Mrazkova, Hana; Lischke, Robert; Špíšek, Radek; Adkins, Irena

doi:10.1371/journal.pone.0171539

Cited by 24 publications

(19 citation statements)

References 44 publications

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“…DCs pulsed with sHS-treated tumor cells stimulated antigen-specific CD4 C T cells and induced higher CD8 C T cell activation and proliferation in vitro T cell stimulatory capacity of DC pulsed with mHS or sHStreated tumor cells was tested in autologous antigen unspecific system and autologous antigen-specific system using HStreated tumor cells that stably express influenza M1 protein as a model antigen. 37 DCs loaded with mHS or sHS-treated tumor cells induced similarly high number of IFNg-producing CD8 C T cells (Fig. 5A) and MP1 58-66 -specific CD8 C T cells detected by the tetramer staining (Fig.…”

Section: Phagocytosis Of Shs-treated Tumor Cells Partially Depends Onmentioning

confidence: 83%

“…On day 7, lymphocytes were re-stimulated with fresh DCs treated accordingly to original samples. After 1 h, Brefeldin A (eBioscience) was added to block the release of IFNg for 5 h. After staining with extracellular antibodies for 20 min, 4 C cells were fixed and permeabilized (Fix-PermBuffer Bioscience), and stained to detect intracellular IFNg or Ki-67 for 30 min at 4 C. To detect MP1 58-66 -specific CD8 C T cells, DCs were pulsed with HS-treated A549 stably expressing influenza matrix protein 1(MP1) 37 and incubated with autologous HLA-A2 C T cells as described above. After 8 d, cells were stained with MP1 58-66 -HLA-A Ã 201 Tetramer-PE (2 mL/sample; MBL International) for 30 min together with CD3-PerCP-Cy5.5, CD4-PE-Cy7, CD8-Alexa Fluor 700 and CD45RO-APC antibodies and analyzed by flow cytometry.…”

Section: Detection Of Antigen-specific Ifng-producing T Cells and Cd4mentioning

confidence: 99%

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Severe, but not mild heat-shock treatment induces immunogenic cell death in cancer cells

et al. 2017

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The mechanisms of immunogenicity underlying mild heat-shock (mHS) treatment < 42°C of tumor cells are largely attributed to the action of heat-shock proteins; however, little is known about the immunogenicity of tumor cells undergoing severe cytotoxic heat-shock treatment (sHS > 43°C). Here, we found that sHS, but not mHS (42°C), induces immunogenic cell death in human cancer cell lines as defined by the induction of ER stress response and ROS generation, cell surface exposure of calreticulin, HSP70 and HSP90, decrease of cell surface CD47, release of ATP and HMGB1. Only sHS-treated tumor cells were efficiently killed and phagocytosed by dendritic cells (DCs), which was partially dependent on cell surface calreticulin. DCs loaded with mHS or sHS-treated tumor cells displayed similar level of maturation and stimulated IFNγ-producing CD8 T cells without any additional adjuvants . However, only DCs loaded with sHS-treated tumor cells stimulated antigen-specific CD4 T cells and induced higher CD8 T-cell activation and proliferation. sHS-treated murine cells also exposed calreticulin, HSP70 and HSP90 and activated higher DC maturation than mHS treated cells. Vaccination with sHS-treated tumor cells elicited protective immunity in mice. In this study, we defined specific conditions for the sHS treatment of human lung and ovarian tumor cells to arrive at optimal ratio between effective cell death, immunogenicity and content of tumor antigens for immunotherapeutic vaccine generation.

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Section: Phagocytosis Of Shs-treated Tumor Cells Partially Depends Onmentioning

confidence: 83%

Section: Detection Of Antigen-specific Ifng-producing T Cells and Cd4mentioning

confidence: 99%

Severe, but not mild heat-shock treatment induces immunogenic cell death in cancer cells

et al. 2017

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“…Moreover, DCs that were loaded with HHP-treated tumor cells exhibited an upregulation of maturation markers, chemotactic migration, and the release of pro-inflammatory interleukins when compared to unloaded DCs. In addition, HHP-treated tumor lysate loaded-DCs were able to activate tumor-specific T cells while also downregulating the number of Treg [137][138][139][140].…”

Section: High Hydrostatic Pressurementioning

confidence: 98%

“…Preliminary results have demonstrated that apoptosis induction by HHP was accompanied by exposure/release of several immunogenic molecules, such as HSP90, HSP70, CRT, ATP, and HMGB1, in human prostate, leukemia, and ovarian tumor cell lines and/or primary tumor cells [137,138]. For that reason, the use of HHP-killed human tumor cells has been tested for DC-based vaccine generation [137][138][139][140]. In these assays, human mo-DCs were co-cultured at a DC/tumor cell ratio of 5:1 with cancer cells that were previously subjected to lethal doses of HHP, and then incubated with poly(I:C) or LPS as maturation stimuli.…”

Section: High Hydrostatic Pressurementioning

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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“…Similarly, the treatment of cancer cells with high hydrostatic pressure enhanced the in vitro uptake and presentation of TAA. This DC-based vaccine inhibited tumor growth of TC1 tumors in mice when combined with docetaxel chemotherapy ( 112 ).…”

Section: Dendritic Cellsmentioning

confidence: 99%

Diamonds in the Rough: Harnessing Tumor-Associated Myeloid Cells for Cancer Therapy

et al. 2018

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Therapeutic approaches that engage immune cells to treat cancer are becoming increasingly utilized in the clinics and demonstrated durable clinical benefit in several solid tumor types. Most of the current immunotherapies focus on manipulating T cells, however, the tumor microenvironment (TME) is abundantly infiltrated by a heterogeneous population of tumor-associated myeloid cells, including tumor-associated macrophages (TAMs), tumor-associated dendritic cells (TADCs), tumor-associated neutrophils (TANs), and myeloid-derived suppressor cells (MDSCs). Educated by signals perceived in the TME, these cells often acquire tumor-promoting properties ultimately favoring disease progression. Upon appropriate stimuli, myeloid cells can exhibit cytoxic, phagocytic, and antigen-presenting activities thereby bolstering antitumor immune responses. Thus, depletion, reprogramming or reactivation of myeloid cells to either directly eradicate malignant cells or promote antitumor T-cell responses is an emerging field of interest. In this review, we briefly discuss the tumor-promoting and tumor-suppressive roles of myeloid cells in the TME, and describe potential therapeutic strategies in preclinical and clinical development that aim to target them to further expand the range of current treatment options.

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Generation of dendritic cell-based vaccine using high hydrostatic pressure for non-small cell lung cancer immunotherapy

Cited by 24 publications

References 44 publications

Severe, but not mild heat-shock treatment induces immunogenic cell death in cancer cells

Severe, but not mild heat-shock treatment induces immunogenic cell death in cancer cells

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

Diamonds in the Rough: Harnessing Tumor-Associated Myeloid Cells for Cancer Therapy

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