Ex vivo dendritic cell generation—A critical comparison of current approaches

Han, Patrick; Hanlon, Douglas; Sobolev, Olga; Chaudhury, Rabib; Edelson, Richard L.

doi:10.1016/bs.ircmb.2019.10.003

Cited by 17 publications

(19 citation statements)

References 283 publications

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“…Some of the compounds identified with this platform have entered clinical trials, either as single agents or in combination with ICIs 61,63 . Similarly, novel approaches to drive ICD have been harnessed for the development of therapeutic DC-based vaccines, which are currently under clinical evaluation 207,208 . Moreover, the systematic assessment of ICD biomarkers such as the expression of CALR or HMGB1 on tumor biopsies may yield useful information for patient stratification (Fig.…”

Section: Discussionmentioning

confidence: 99%

Detection of immunogenic cell death and its relevance for cancer therapy

et al. 2020

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Chemotherapy, radiation therapy, as well as targeted anticancer agents can induce clinically relevant tumor-targeting immune responses, which critically rely on the antigenicity of malignant cells and their capacity to generate adjuvant signals. In particular, immunogenic cell death (ICD) is accompanied by the exposure and release of numerous damage-associated molecular patterns (DAMPs), which altogether confer a robust adjuvanticity to dying cancer cells, as they favor the recruitment and activation of antigen-presenting cells. ICD-associated DAMPs include surface-exposed calreticulin (CALR) as well as secreted ATP, annexin A1 (ANXA1), type I interferon, and high-mobility group box 1 (HMGB1). Additional hallmarks of ICD encompass the phosphorylation of eukaryotic translation initiation factor 2 subunit-α (EIF2S1, better known as eIF2α), the activation of autophagy, and a global arrest in transcription and translation. Here, we outline methodological approaches for measuring ICD markers in vitro and ex vivo for the discovery of next-generation antineoplastic agents, the development of personalized anticancer regimens, and the identification of optimal therapeutic combinations for the clinical management of cancer.

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Section: Discussionmentioning

confidence: 99%

Detection of immunogenic cell death and its relevance for cancer therapy

et al. 2020

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“…All animal studies were approved by the Laboratory Animal Welfare and Ethics Committee of the Third Military Medical University. DCs were isolated from mouse bone marrow as previously described with slight modifications (19,20). Balb/C mice (age, 6-8 weeks; weight, 20-25 g; n=80) were provided by the Experimental Animal Center of Daping Hospital.…”

Section: Methodsmentioning

confidence: 99%

E6‑regulated overproduction of prostaglandin�E2 may inhibit migration of dendritic cells in human papillomavirus 16‑positive cervical lesions

et al. 2020

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Continuous human papillomavirus (HPV) infection is a critical cause of cervical lesions; however, the specific mechanism is currently not clear. E6 is one of the most important oncoproteins associated with HPV, which regulates synthases in the production of prostaglandin E2 (PGE 2 ). Notably, PGE 2 has been reported to be upregulated in cervical lesions. An insufficient number of mature dendritic cells (DCs), which is unable to cause an effective immune response, is an important cause of cervical lesions. Therefore, this study explored the possible causes of HPV16-positive cervical lesions by identifying the relationship between E6, PGE 2 and DCs. Firstly, the distribution and status of DCs in clinical biopsy specimens and animal models were analyzed with immunohistochemistry and flow cytometry, which demonstrated that the migratory ability of DCs was inhibited in HPV16-positive cervical lesions. Furthermore, using immunohistochemistry, western blotting and ELISA, it was revealed that as the degree of cervical lesions increased, the expression of PGE 2 and its synthases increased. Subsequently, as determined using Transwell and 3D migration assays, it was revealed that a high concentration of PGE 2 inhibited the migration of DCs, which may explain the phenomenon observed in cervical lesions. Notably, E6 was identified to regulate PGE 2 expression. The in vivo experiments indicated that E6 may increase the expression levels of PGE 2 in cervical lesions, which could eventually induce inhibition of the migration of DCs. In conclusion, the present study suggested that E6 regulated overproduction of PGE 2 , which may induce inhibition of DC migration in HPV16-positive cervical lesions.

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“…All experiments conformed to the guidelines of ethical use of animals, and all efforts were made to minimize animal suffering and reduce the number of animals used. dcs were isolated from mouse bone marrow as previously described with slight modifications (13,14). C57BL/6 mice (male; age, 6-8 weeks; weight, 20-25 g; n=40) were provided by the Experimental Animal center of daping Hospital, Third Military Medical University.…”

Section: Methodsmentioning

confidence: 99%

Prostaglandin E2 serves a dual role in regulating the migration of dendritic cells

et al. 2020

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dendritic cells (dcs) are the most potent antigen-presenting cells, and are indispensable in the immune system. Prostaglandin E2 (PGE 2) has been demonstrated to modulate the migration of dcs, but with inconsistent results. The present study, based on our previous research, used murine bone marrow-derived dcs to elucidate the potential regulatory mechanism of PGE 2 on the migration of dcs. The results indicated that PGE 2 served a dual role in regulating the migration of dcs in a dose-dependent manner. High concentrations of PGE 2 inhibited cell migration, whereas low concentrations exhibited the opposite effect. Flow cytometry revealed that the expression of cc chemokine receptor type 7 on the dc surface was increased following treatment with low concentrations of PGE 2 and slightly decreased by high concentrations of PGE 2. The effect of PGE 2 was indicated to be exerted via reorganizing the F-actin cytoskeleton using confocal microscopy. Moreover, the regulatory effect of PGE 2 on the migration of dcs was validated in vivo. Subsequent gene expression profile analyses using RNA-sequencing technology indicated that PGE 2 induced alterations in the expression of multiple downstream genes and signaling pathway molecules associated with cell migration and the cytoskeleton. These findings may provide an improved understanding on the mechanism of dc migration under both pathological and physiological conditions. Moreover, the biological implications of these findings may provide a novel perspective of the immunological surveillance in the progression of different types of diseases.

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Ex vivo dendritic cell generation—A critical comparison of current approaches

Cited by 17 publications

References 283 publications

Detection of immunogenic cell death and its relevance for cancer therapy

Detection of immunogenic cell death and its relevance for cancer therapy

E6‑regulated overproduction of prostaglandin�E2 may inhibit migration of dendritic cells in human papillomavirus 16‑positive cervical lesions

Prostaglandin E2 serves a dual role in regulating the migration of dendritic cells

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