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The Role of Dendritic Cell in Cancers and Immune Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (20 January 2023) | Viewed by 10843

Special Issue Editors

Osteoncology and Rare Tumors Center, Immunotherapy, Cell Therapy and Biobank, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
Interests: dendritic cells; advanced therapy medicinal products; TIL; quality control test; flow cytometry; potency test; GMP regulation
Special Issues, Collections and Topics in MDPI journals
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (FC), Italy
Interests: cancer immunotherapy; dendritic cell; TIL; adoptive cell therapies; skin cancers

Special Issue Information

Dear Colleagues,

Dendritic cells (DCs) are the most efficient antigen-presenting cells, and thus play a central role in immunity. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and the adaptive immune systems. Their ability to generate specific anti-tumor T cells, able to infiltrate the tumor bed and kill the target cells through cytolytic mechanisms (i.e., perforin and granzyme B), has led to the use of dendritic cells loaded with tumor antigens in several clinical studies.

Moreover, the modulation of DCs can lead to defective or dysregulated T-cell-mediated immunity and subsequently decreased resistance to infectious disease, or, conversely, increased incidence of allergies or autoimmune disease. Improved knowledge on the role of the altered distribution and/or incorrect functionality of DCs may lead to an improvement in therapy for these autoimmune diseases.

In this Special Issue, we invite contributions in the form of original research articles, reviews, or shorter perspective articles on all aspects related to dendritic cells and the themes above.

Dr. Massimiliano Petrini
Dr. Laura Ridolfi
Guest Editors

Manuscript Submission Information

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Keywords

  • DCs and tumor immunotherapy
  • immune modulation
  • mechanisms of action
  • clinical trials
  • future perspectives for DC-based therapy
  • adoptive immunotherapy and DCS
  • regulatory aspects for DC generation

Published Papers (7 papers)

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Research

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17 pages, 3270 KiB  
Article
Dendritic Cell Subpopulations Are Associated with Morphological Features of Breast Ductal Carcinoma In Situ
Int. J. Mol. Sci. 2023, 24(12), 9918; https://doi.org/10.3390/ijms24129918 - 08 Jun 2023
Cited by 1 | Viewed by 1080
Abstract
Ductal carcinoma in situ (DCIS) is the preinvasive form of breast cancer (BC). It is disputed whether all cases of DCIS require extensive treatment as the overall risk of progression to BC is estimated at 40%. Therefore, the crucial objective for researchers is [...] Read more.
Ductal carcinoma in situ (DCIS) is the preinvasive form of breast cancer (BC). It is disputed whether all cases of DCIS require extensive treatment as the overall risk of progression to BC is estimated at 40%. Therefore, the crucial objective for researchers is to identify DCIS with significant risk of transformation into BC. Dendritic cells (DC) are professional antigen presenting cells and as such play a pivotal role in the formation of immune cells that infiltrate in breast tumors. The aim of this study was to investigate the relationship between the density of DCs with different superficial antigens (CD1a, CD123, DC-LAMP, DC-SIGN) and various histopathological characteristics of DCIS. Our evaluation indicated that CD123+ and DC-LAMP+ cells were strongly associated with maximal tumor size, grading and neoductgenesis. Together with CD1a+ cells, they were negatively correlated with hormonal receptors expression. Furthermore, the number of DC-LAMP+ cells was higher in DCIS with comedo necrosis, ductal spread, lobular cancerization as well as comedo-type tumors, while CD1a+ cells were abundant in cases with Paget disease. We concluded that different subpopulations of DCs relate to various characteristics of DCIS. Of the superficial DCs markers, DC-LAMP seems particularly promising as a target for further research in this area. Full article
(This article belongs to the Special Issue The Role of Dendritic Cell in Cancers and Immune Diseases)
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20 pages, 6881 KiB  
Article
Distribution of DC Subtypes: CD83+, DC-LAMP+, CD1a+, CD1c+, CD123+, and DC-SIGN+ in the Tumor Microenvironment of Endometrial Cancers—Correlation with Clinicopathologic Features
Int. J. Mol. Sci. 2023, 24(3), 1933; https://doi.org/10.3390/ijms24031933 - 18 Jan 2023
Viewed by 1326
Abstract
Treatment options for endometrial cancer (EC) do not provide satisfactory survival improvement for advanced cases, hence the interest in novel therapies utilizing immunological regulatory mechanisms. Measures to modify the functionality of dendritic cells (DCs) found in TME are intensively investigated, given that DCs [...] Read more.
Treatment options for endometrial cancer (EC) do not provide satisfactory survival improvement for advanced cases, hence the interest in novel therapies utilizing immunological regulatory mechanisms. Measures to modify the functionality of dendritic cells (DCs) found in TME are intensively investigated, given that DCs play a crucial role in inducing antitumor immunity. Samples of malignant endometrial neoplasms obtained from 94 patients were immunohistochemically stained with selected antibodies. Counts of positively identified DCs were correlated with clinical advancement and histological malignancy of cancers. The most prominent DC subtypes were immature DC-SIGN+ or CD123+. Mature CD83+ DCs were the fewest. We found a significant divergence of grade value distribution between cancers of different DCs’ CD1a+ counts. The DC-LAMP+ count was positively associated with grade. Cancers with the least DC CD1c+ or DC CD123+ had higher pT scores than ones that were more heavily infiltrated. ECs can suppress immune cells, hence the predominance of immature DCs in our samples. Associations between DC counts and clinicopathological features of EC were observed only for a few subsets, which was plausibly due to the low diversity of the obtained samples or the small group size. Predictive abilities of particular DC immune subsets within EC’s TME remain ambiguous, which calls for further research. Full article
(This article belongs to the Special Issue The Role of Dendritic Cell in Cancers and Immune Diseases)
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7 pages, 967 KiB  
Communication
Human Monocyte-Derived Dendritic Cells Are the Pharmacological Target of the Immunosuppressant Flavonoid Silibinin
Int. J. Mol. Sci. 2022, 23(18), 10417; https://doi.org/10.3390/ijms231810417 - 08 Sep 2022
Cited by 1 | Viewed by 1194
Abstract
Silibinin, a natural polyphenolic flavonoid, is known to possess anti-inflammatory, anticancer, antioxidant, and immunomodulatory properties. However, the effects of Silibinin on the maturation and immunostimulatory functions of human dendritic cells (DC) remain to be elucidated. In this study, we have attempted to ascertain [...] Read more.
Silibinin, a natural polyphenolic flavonoid, is known to possess anti-inflammatory, anticancer, antioxidant, and immunomodulatory properties. However, the effects of Silibinin on the maturation and immunostimulatory functions of human dendritic cells (DC) remain to be elucidated. In this study, we have attempted to ascertain whether Silibinin influences the maturation, cytokine production, and antigen-presenting capacity of human monocyte-derived DC. We show that Silibinin significantly suppresses the upregulation of costimulatory and MHC molecules in LPS-stimulated mature DC and inhibits lipopolysaccharide (LPS)-induced interleukin (IL)-12, IL-23, and TNF-α production. Furthermore, Silibinin impairs the proliferation response of the allogenic memory CD4 T lymphocytes elicited by LPS-matured DC and their Th1/Th17 profile. These findings demonstrate that Silibinin displays immunosuppressive activity by inhibiting the maturation and activation of human DC and support its potential application of adjuvant therapy in the treatment of autoimmune diseases. Full article
(This article belongs to the Special Issue The Role of Dendritic Cell in Cancers and Immune Diseases)
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13 pages, 3222 KiB  
Article
Wasabi Component 6-(Methylsulfinyl)hexly Isothiocyanate and Derivatives Improve the Survival of Skin Allografts
Int. J. Mol. Sci. 2022, 23(15), 8488; https://doi.org/10.3390/ijms23158488 - 30 Jul 2022
Viewed by 1441
Abstract
We tested the effect of 6-(Methylsulfinyl)hexyl Isothiocyanate (6-MITC) and derivatives (I7447 and I7557) on the differentiation and maturation of human myeloid dendritic cells (DCs) in vitro, and skin transplantation in vivo. Triggering of CD14+ myeloid monocyte development toward myeloid DCs with and [...] Read more.
We tested the effect of 6-(Methylsulfinyl)hexyl Isothiocyanate (6-MITC) and derivatives (I7447 and I7557) on the differentiation and maturation of human myeloid dendritic cells (DCs) in vitro, and skin transplantation in vivo. Triggering of CD14+ myeloid monocyte development toward myeloid DCs with and without 6-MITC and derivatives to examine the morphology, viability, surface marker expression, and cytokine production. Stimulatory activity on allogeneic naive T cells was measured by proliferation and interferon-γ production. The skin allograft survival area model was used to translate the 6-MITC and derivatives’ antirejection effect. All of the compounds had no significant effects on DC viability and reduced the formation of dendrites at concentrations higher than 10 μM. At this concentration, 6-MITC and I7557, but not I7447, inhibited the expression of CD1a and CD83. Both 6-MITC and I7557 exhibited T-cells and interferon-γ augmentation at lower concentrations and suppression at higher concentration. The 6-MITC and I7557 prolonged skin graft survival. Both the 6-MITC and I7557 treatment resulted in the accumulation of regulatory T cells in recipient rat spleens. No toxicity was evident in 6-MITC and I7557 treatment. The 6-MITC and I7557 induced human DC differentiation toward a tolerogenic phenotype and prolonged rat skin allograft survival. These compounds may be effective as immunosuppressants against transplant rejection. Full article
(This article belongs to the Special Issue The Role of Dendritic Cell in Cancers and Immune Diseases)
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15 pages, 2250 KiB  
Article
Presence of Dendritic Cell Subsets in Sentinel Nodes of Breast Cancer Patients Is Related to Nodal Burden
Int. J. Mol. Sci. 2022, 23(15), 8461; https://doi.org/10.3390/ijms23158461 - 30 Jul 2022
Cited by 2 | Viewed by 1449
Abstract
BACKGROUND: Sentinel lymph nodes (SLNs) are both the first site where breast cancer (BC) metastases form and where anti-tumoral immunity develops. Despite being the most potent antigen-presenting cells, dendritic cells (DCs) located in a nodal tissue can both promote or suppress immune response [...] Read more.
BACKGROUND: Sentinel lymph nodes (SLNs) are both the first site where breast cancer (BC) metastases form and where anti-tumoral immunity develops. Despite being the most potent antigen-presenting cells, dendritic cells (DCs) located in a nodal tissue can both promote or suppress immune response against cancer in SLNs. METHODS: In SLNs excisions obtained from 123 invasive BC patients, we performed immunohistochemistry (IHC) for CD1a, CD1c, DC-LAMP, and DC-SIGN to identify different DCs populations. Then we investigated the numbers of DCs subsets in tumor-free, micrometastatic, and macrometastatic SLNs with the use of a light microscope. RESULTS: We observed that CD1c+ and DC-SIGN+ DCs were more numerous in SLNs with a larger tumor size. More abundant intratumoral DC-LAMP+ population was related to a higher number of metastatic lymph nodes. Conversely, more abundant CD1a+ DCs were associated with a decreasing nodal burden in SLNs and a lower number of involved lymph nodes. Moreover, densities of the investigated DC populations differed with respect to tumor grade, HER2 overexpression, hormone receptor status, and histologic type of BC. CONCLUSIONS: According to their subtype, DCs are associated with either lower or higher nodal burden in SLNs from invasive BC patients. These relationships appear to be dependent not only on the maturation state of DCs but also on the histological and biological characteristics of the tumor. Full article
(This article belongs to the Special Issue The Role of Dendritic Cell in Cancers and Immune Diseases)
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Review

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13 pages, 11065 KiB  
Review
Different Roles of Dendritic Cells for Chronic Rhinosinusitis Treatment According to Phenotype
Int. J. Mol. Sci. 2022, 23(14), 8032; https://doi.org/10.3390/ijms23148032 - 21 Jul 2022
Cited by 1 | Viewed by 1991
Abstract
Dendritic cells (DCs) are antigen-presenting cells derived from the bone marrow that play an important role in the association between the innate and adaptive immune responses. The onset and development of chronic rhinosinusitis (CRS) involve a serious imbalance in immune regulation and mechanical [...] Read more.
Dendritic cells (DCs) are antigen-presenting cells derived from the bone marrow that play an important role in the association between the innate and adaptive immune responses. The onset and development of chronic rhinosinusitis (CRS) involve a serious imbalance in immune regulation and mechanical dysfunction caused by an abnormal remodeling process. Recent studies have shown that an increase in DCs in CRS and their function of shaping the nasal mucosal immune response may play an important role in the pathogenesis of CRS. In this review, we discuss DC subsets in mice and humans, as well as the function of DCs in the nasal sinus mucosa. In addition, the mechanism by which DCs can be used as targets for therapeutic intervention for CRS and potential future research directions are also discussed. Full article
(This article belongs to the Special Issue The Role of Dendritic Cell in Cancers and Immune Diseases)
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Other

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8 pages, 4378 KiB  
Case Report
Angioimmunoblastic T-Cell Lymphoma with Exuberant CD30-Positive Follicular Dendritic Cell Proliferation in a SARS-CoV-2 Patient: The Role of Mutational Analysis to Exclude an Associated Follicular Dendritic Cell Sarcoma
Int. J. Mol. Sci. 2022, 23(16), 9349; https://doi.org/10.3390/ijms23169349 - 19 Aug 2022
Cited by 2 | Viewed by 1420
Abstract
Follicular dendritic cell (FDC) proliferation in angioimmunoblastic T-cell lymphoma (AITL) is still not well defined, challenging the accurate differential diagnosis between the AITL with expanded follicular dendritic cell meshwork and the combined AITL and follicular dendritic cell sarcoma (FDCS). Herein, we reported the [...] Read more.
Follicular dendritic cell (FDC) proliferation in angioimmunoblastic T-cell lymphoma (AITL) is still not well defined, challenging the accurate differential diagnosis between the AITL with expanded follicular dendritic cell meshwork and the combined AITL and follicular dendritic cell sarcoma (FDCS). Herein, we reported the case of a 58-year-old male with coexisting SARS-CoV-2 infection and AITL with an exuberant CD30-positive FDC proliferation, in which genetic analysis identified mutations of genes commonly involved in AITL but not in FDC sarcoma (i.e., RHOA, TET2, DNMT3A, and IDH2), thus supporting the reactive nature of the CD30-positive FDC expansion. Full article
(This article belongs to the Special Issue The Role of Dendritic Cell in Cancers and Immune Diseases)
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