scholarly journals Use of Dendritic Cell Receptors as Targets for Enhancing Anti-Cancer Immune Responses

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 418 ◽  
Author(s):  
Md Hossain ◽  
Katherine Wall
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Immune Responses ◽  
Specific Antigen ◽  
Intercellular Adhesion Molecule ◽  
Thymic Epithelial Cell ◽  
Antigen Uptake ◽  
Cell Receptors ◽  
Mhc Molecules ◽  
Anti Cancer

A successful anti-cancer vaccine construct depends on its ability to induce humoral and cellular immunity against a specific antigen. Targeting receptors of dendritic cells to promote the loading of cancer antigen through an antibody-mediated antigen uptake mechanism is a promising strategy in cancer immunotherapy. Researchers have been targeting different dendritic cell receptors such as Fc receptors (FcR), various C-type lectin-like receptors such as dendritic and thymic epithelial cell-205 (DEC-205), dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), and Dectin-1 to enhance the uptake process and subsequent presentation of antigen to T cells through major histocompatibility complex (MHC) molecules. In this review, we compare different subtypes of dendritic cells, current knowledge on some important receptors of dendritic cells, and recent articles on targeting those receptors for anti-cancer immune responses in mouse models.

scholarly journals CD1 and Major Histocompatibility Complex II Molecules Follow a Different Course during Dendritic Cell Maturation

2003 ◽  
Vol 14 (8) ◽  
pp. 3378-3388 ◽  
Author(s):  
Nicole N. van der Wel ◽  
Masahiko Sugita ◽  
Donna M. Fluitsma ◽  
Xaiochun Cao ◽  
Gerty Schreibelt ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
Dendritic Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Dendritic Cell Maturation ◽  
Cell Maturation ◽  
Major Histocompatibility ◽  
Mhc Molecules ◽  
Histocompatibility Complex

The maturation of dendritic cells is accompanied by the redistribution of major histocompatibility complex (MHC) class II molecules from the lysosomal MHC class II compartment to the plasma membrane to mediate presentation of peptide antigens. Besides MHC molecules, dendritic cells also express CD1 molecules that mediate presentation of lipid antigens. Herein, we show that in human monocyte-derived dendritic cells, unlike MHC class II, the steady-state distribution of lysosomal CD1b and CD1c isoforms was unperturbed in response to lipopolysaccharide-induced maturation. However, the lysosomes in these cells underwent a dramatic reorganization into electron dense tubules with altered lysosomal protein composition. These structures matured into novel and morphologically unique compartments, here termed mature dendritic cell lysosomes (MDL). Furthermore, we show that upon activation mature dendritic cells do not lose their ability of efficient clathrin-mediated endocytosis as demonstrated for CD1b and transferrin receptor molecules. Thus, the constitutive endocytosis of CD1b molecules and the differential sorting of MHC class II from lysosomes separate peptide- and lipid antigen-presenting molecules during dendritic cell maturation.

scholarly journals Regulation of the Migration of Distinct Dendritic Cell Subsets

2021 ◽  
Vol 9 ◽  
Author(s):  
Meng Feng ◽  
Shuping Zhou ◽  
Yong Yu ◽  
Qinghong Su ◽  
Xiaofan Li ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Immune Responses ◽  
The Body ◽  
Inflammatory Factors ◽  
Pathogenic Microorganisms ◽  
Migration Patterns ◽  
Dendritic Cell Subsets ◽  
And Migration ◽  
Antigen Presenting

Dendritic cells (DCs), a class of antigen-presenting cells, are widely present in tissues and apparatuses of the body, and their ability to migrate is key for the initiation of immune activation and tolerogenic immune responses. The importance of DCs migration for their differentiation, phenotypic states, and immunologic functions has attracted widespread attention. In this review, we discussed and compared the chemokines, membrane molecules, and migration patterns of conventional DCs, plasmocytoid DCs, and recently proposed DC subgroups. We also review the promoters and inhibitors that affect DCs migration, including the hypoxia microenvironment, tumor microenvironment, inflammatory factors, and pathogenic microorganisms. Further understanding of the migration mechanisms and regulatory factors of DC subgroups provides new insights for the treatment of diseases, such as infection, tumors, and vaccine preparation.

DC-SIGN (dendritic cell-specific ICAM-grabbing non-integrin) and DC-SIGN-related (DC-SIGNR): friend or foe?

2003 ◽  
Vol 104 (4) ◽  
pp. 437-446 ◽  
Author(s):  
Elizabeth J. SOILLEUX
Keyword(s):  
Endothelial Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
T Lymphocytes ◽  
High Efficiency ◽  
Immunoglobulin E ◽  
Expression Patterns ◽  
Intercellular Adhesion Molecule ◽  
Carbohydrate Binding ◽  
Wide Range

C-type lectins are calcium-dependent carbohydrate-binding proteins with a wide range of biological functions, many of which are related to immunity. DC-SIGN (dendritic cell-specific ICAM-grabbing non-integrin, where ICAM is intercellular adhesion molecule) is a recently described mannose-specific C-type lectin expressed by dendritic cells. Dendritic cells are potent antigen-presenting cells capable of activating T-lymphocytes. DC-SIGN, which is expressed by dendritic cells, binds to ICAM-3 on T-lymphocytes, therefore playing an important role in the activation of T-lymphocytes. DC-SIGN can also bind HIV, and the virus may remain bound to DC-SIGN for protracted periods. DC-SIGN may deliver bound HIV to permissive cell types, mediating infection with high efficiency. A closely related C-type lectin, DC-SIGN-related molecule (DC-SIGNR) has also been described. DC-SIGNR is expressed by restricted subsets of endothelial cells, but has similar ICAM-3 and HIV-binding properties to DC-SIGN. This review describes the mapping of DC-SIGN and DC-SIGNR to chromosome 19p13.3 adjacent to the previously described C-type lectin, CD23 [the low-affinity receptor for immunoglobulin E (FcERII)]. The similar genomic organization of these three genes is discussed and consideration is given to the evolutionary duplications that may underlie this arrangement. Both DC-SIGN and DC-SIGNR possess a neck region, made up of multiple repeats, which supports the ligand-binding domain. Consideration is given to the biological reasons underlying the considerable polymorphism in the numbers of repeats in DC-SIGNR, but not DC-SIGN. The expression patterns of both DC-SIGN and DC-SIGNR are discussed in detail, with particular attention to the expression of both molecules in the placenta, which may have implications for the vertical transmission of HIV. Since dendritic cells may be important in determining the phenotype of many immune responses, via effects on T-lymphocytes, the differential expression of DC-SIGN by particular dendritic cell subsets may have important implications for the immunobiological functions of DC-SIGN. Similarly, the expression of DC-SIGNR by very restricted subsets of endothelial cells may give clues to the function of DC-SIGNR. Finally, the role of DC-SIGN in pathology, particularly in infective and neoplastic processes, is discussed, followed by speculation about likely future developments in this field.

scholarly journals Interaction of classical swine fever virus with dendritic cells

2004 ◽  
Vol 85 (6) ◽  
pp. 1633-1641 ◽  
Author(s):  
C. P. Carrasco ◽  
R. C. Rigden ◽  
I. E. Vincent ◽  
C. Balmelli ◽  
M. Ceppi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Classical Swine Fever Virus ◽  
Specific Antigen ◽  
Classical Swine Fever ◽  
Fever Virus ◽  
Immune Reactivity ◽  
Type I ◽  
Antigen Uptake ◽  
Polycytidylic Acid

Functional disruption of dendritic cells (DCs) is an important strategy for viral pathogens to evade host defences. Monocytotropic viruses such as classical swine fever virus (CSFV) could employ such a mechanism, since the virus can suppress immune responses and induce apoptosis without infecting lymphocytes. Here, CSFV was shown to infect and efficiently replicate in monocyte- and in bone marrow-derived DCs. Interestingly, the infected DCs displayed neither modulated MHC nor CD80/86 expression. Stimulation of DCs with IFN-α/TNF-α or polyinosinic–polycytidylic acid (pIC) induced phenotypic maturation with increased MHC and CD80/86 expression, both with mock-treated and infected DCs. In addition, the T cell stimulatory capacity of CSFV-infected DCs was maintained both in a polyclonal T cell stimulation and in specific antigen-presentation assays, requiring antigen uptake and processing. Interestingly, similar to macrophages, CSFV did not induce IFN-α responses in these DCs and even suppressed pIC-induced IFN-α induction. Other cytokines including interleukin (IL)-6, IL-10, IL-12 and TNF-α were not modulated. Taken together, these results demonstrated that CSFV can replicate in DCs and control IFN type I responses, without interfering with the immune reactivity. These results are interesting considering that DC infection with RNA viruses usually results in DC activation.

scholarly journals Effects of Fatty Acid Oxidation and Its Regulation on Dendritic Cell-Mediated Immune Responses in Allergies: An Immunometabolism Perspective

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Shanfeng Sun ◽  
Yanjun Gu ◽  
Junjuan Wang ◽  
Cheng Chen ◽  
Shiwen Han ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Fatty Acid ◽  
Dendritic Cell ◽  
Immune Responses ◽  
Fatty Acid Oxidation ◽  
Cell Activation ◽  
Metabolic Reprogramming ◽  
Acid Oxidation ◽  
Dendritic Cell Activation ◽  
Functional Changes

Type 1 allergies, involve a complex interaction between dendritic cells and other immune cells, are pathological type 2 inflammatory immune responses against harmless allergens. Activated dendritic cells undergo extensive phenotypic and functional changes to exert their functions. The activation, differentiation, proliferation, migration, and mounting of effector reactions require metabolic reprogramming. Dendritic cells are important upstream mediators of allergic responses and are therefore an important effector of allergies. Hence, a better understanding of the underlying metabolic mechanisms of functional changes that promote allergic responses of dendritic cells could improve the prevention and treatment of allergies. Metabolic changes related to dendritic cell activation have been extensively studied. This review briefly outlines the basis of fatty acid oxidation and its association with dendritic cell immune responses. The relationship between immune metabolism and effector function of dendritic cells related to allergic diseases can better explain the induction and maintenance of allergic responses. Further investigations are warranted to improve our understanding of disease pathology and enable new treatment strategies.

scholarly journals Measles Virus Targets DC-SIGN To Enhance Dendritic Cell Infection

2006 ◽  
Vol 80 (7) ◽  
pp. 3477-3486 ◽  
Author(s):  
Lot de Witte ◽  
Marion Abt ◽  
Sibylle Schneider-Schaulies ◽  
Yvette van Kooyk ◽  
Teunis B. H. Geijtenbeek
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Respiratory Tract ◽  
Immune Suppression ◽  
Measles Virus ◽  
Viral Transmission ◽  
Intercellular Adhesion Molecule ◽  
Wild Type ◽  
Cell Infection ◽  
Specific Receptors

ABSTRACT Dendritic cells (DCs) are involved in the pathogenesis of measles virus (MV) infection by inducing immune suppression and possibly spreading the virus from the respiratory tract to lymphatic tissues. It is becoming evident that DC function can be modulated by the involvement of different receptors in pathogen interaction. Therefore, we have investigated the relative contributions of different MV-specific receptors on DCs to MV uptake into and infection of these cells. DCs express the MV receptors CD46 and CD150, and we demonstrate that the C-type lectin DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is a novel receptor for laboratory-adapted and wild-type MV strains. The ligands for DC-SIGN are both MV glycoproteins F and H. In contrast to CD46 and CD150, DC-SIGN does not support MV entry, since DC-SIGN does not confer susceptibility when stably expressed in CHO cells. However, DC-SIGN is important for the infection of immature DCs with MV, since both attachment and infection of immature DCs with MV are blocked in the presence of DC-SIGN inhibitors. Our data demonstrate that DC-SIGN is crucial as an attachment receptor to enhance CD46/CD150-mediated infection of DCs in cis. Moreover, MV might not only target DC-SIGN to infect DCs but may also use DC-SIGN for viral transmission and immune suppression.

scholarly journals Anti-CD27 Antibody Potentiates Antitumor Effect of Dendritic Cell–Based Vaccine in Prostate Cancer–Bearing Mice

2015 ◽  
Vol 100 (1) ◽  
pp. 155-163 ◽  
Author(s):  
Si-Ming Wei ◽  
Jin-Xuan Fei ◽  
Feng Tao ◽  
Hang-Li Pan ◽  
Qing Shen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Monoclonal Antibody ◽  
Cell Proliferation ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Immune Responses ◽  
Antitumor Effect ◽  
T Cell Proliferation ◽  
Tumor Lysate ◽  
Dendritic Cell Based Vaccine

Abstract In the current study, we investigated whether anti-CD27 monoclonal antibody can enhance the antitumor efficacy of a dendritic cell–based vaccine in prostate cancer–bearing mice. The overall therapeutic effect of a dendritic cell–based vaccine for prostate cancer remains moderate. A prostate cancer model was established by subcutaneous injection of RM-1 tumor cells into male C57BL/6 mice on day 0. After 4 days, tumor-bearing mice were treated with RM-1 tumor lysate–pulsed dendritic cells (i.e., dendritic cell–based vaccine), anti-CD27 monoclonal antibody, or a combination of RM-1 tumor lysate–pulsed dendritic cells with anti-CD27 monoclonal antibody. Mice were killed at 21 days after tumor cell implantation. Tumor size was measured for assessment of antitumor effect. Spleens were collected for analysis of antitumor immune responses. The antitumor immune responses were evaluated by measuring the proliferation and activity of T cells, which have the ability to kill tumor cells. The combination therapy with RM-1 tumor lysate–pulsed dendritic cells and anti-CD27 antibody significantly enhanced T-cell proliferation and activity, and significantly reduced tumor growth, compared with monotherapy with RM-1 tumor lysate–pulsed dendritic cells or anti-CD27 antibody. Our results suggest that combined treatment can strengthen antitumor efficacy by improving T-cell proliferation and activity.

Immunosuppressive properties of CD95L-transduced “killer” hybrids created by fusing donor- and recipient-derived dendritic cells

Blood ◽  
2001 ◽  
Vol 98 (12) ◽  
pp. 3465-3472 ◽  
Author(s):  
Hiroyuki Matsue ◽  
Keiko Matsue ◽  
Masahiro Kusuhara ◽  
Tadashi Kumamoto ◽  
Ko Okumura ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Organ Transplantation ◽  
Mhc Class I ◽  
Hematopoietic Cell Transplantation ◽  
Class Ii ◽  
Class I ◽  
Delayed Type Hypersensitivity ◽  
Mhc Molecules ◽  
Dc Line

Abstract Allogeneic immune responses, which are initiated by dendritic cells (DCs) of both donor and host origins, remain a major obstacle in organ transplantation. Presentation of intact major histocompatibility complex (MHC) molecules by allogeneic DCs and allogeneic peptides by syngeneic DCs leads to complex allogeneic immune responses. This study reports a novel strategy designed to suppress both pathways. A stable DC line XS106 (A/J mouse origin) was transfected with CD95L cDNA and fused with splenic DCs purified from allogeneic BALB/c mice. The resulting “killer” DC-DC hybrids: (1) expressed CD95L and MHC class I and class II molecules of both A/J and BALB/c origins, while maintaining otherwise characteristic surface phenotypes of mature DCs; (2) inhibited MHC class I– and class II–restricted mixed leukocyte reactions between the parental strains by triggering apoptosis of alloreactive T cells; and (3) abolished delayed-type hypersensitivity responses of A/J (and BALB/c) mice to BALB/c-associated (and A/J-associated) alloantigens when injected intravenously into A/J (and BALB/c) mice. The onset of graft-versus-host disease in (BALB/c × A/J) F1 hosts receiving A/J-derived hematopoietic cell transplantation was suppressed significantly (P < .001) by killer DC-DC hybrid treatment. These results form both technical and conceptual frameworks for clinical applications of CD95L-transduced killer hybrids created between donor DCs and recipient DCs in the prevention of allogeneic immune responses following organ transplantation.

Sign in / Sign up

Export Citation Format

Share Document