The immune checkpoint inhibitors have revolutionized cancer immunotherapy. These inhibitors are game changers in many cancers and for many patients, sometimes show unprecedented therapeutic efficacy. However, their therapeutic efficacy is largely limited in many solid tumors where the tumor-controlled immune microenvironment prevents the immune system from efficiently reaching, recognizing, and eliminating cancer cells. The tumor immune microenvironment is largely orchestrated by immune cells through which tumors gain resistance against the immune system. Among these cells are mast cells and dendritic cells. Both cell types possess enormous capabilities to shape the immune microenvironment. These capabilities stage these cells as cellular checkpoints in the immune microenvironment. Regaining control over these cells in the tumor microenvironment can open new avenues for breaking the resistance of solid tumors to immunotherapy. In this review, we will discuss mast cells and dendritic cells in the context of solid tumors and how these immune cells can, alone or in cooperation, modulate the solid tumor resistance to the immune system. We will also discuss how this modulation could be used in novel immunotherapeutic modalities to weaken the solid tumor resistance to the immune system. This weakening could then help other immunotherapeutic modalities engage against these tumors more efficiently.

• Klíčová slova
• cellular checkpoint, dendritic cells, immunotherapy, mast cells,
• MeSH
• dendritické buňky patologie   MeSH
• imunoterapie MeSH
• inhibitory kontrolních bodů MeSH
• lidé MeSH
• mastocyty * patologie   MeSH
• nádorové mikroprostředí MeSH
• nádory * patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• inhibitory kontrolních bodů MeSH

We evaluated dendritic cells (DC), regulatory T lymphocytes (Treg) and neutrophils in 37 patients with newly diagnosed renal cell carcinoma (RCC) in the tumor and peripheral blood (PB) and correlated these parameters with tumor staging (early-T1, 2, late-T3, 4 and metastatic disease). The number of myeloid and plasmacytoid DC in blood of RCC patients was higher than in healthy controls. The percentage of myeloid dendritic cells (mDC) from CD45+ cells in tumors was higher in comparison with peripheral blood irrespective of disease stage. Higher percentage of these cells expressed a maturation marker in the periphery in the early stage (CD83 expressing cells). The number of plasmacytoid dendritic cells (pDC) in PB was similar in both early and late stage groups, but the early group displayed a significantly higher percentage of pDC in tumor cell suspension. Neutrophil counts in the peripheral blood of RCC patients were higher than in healthy controls, but the counts in both tumor stage groups were similar. The proportion of neutrophils from CD45+ cells was higher in late stage tumors. Higher percentage of Treg from CD4+ cells was detected in renal carcinoma tissue in comparison to PB with no difference between stages of the disease. Our results reflect the complex interplay between various cells of the immune system and the tumor microenvironment. Activation of dendritic cell subpopulations at early stages of the disease course is counterbalanced by the early appearance of T regulatory cells both in the periphery and tumor tissue. Later stages are characterized by the accumulation of neutrophils in the tumor. Appropriate timing of anticancer strategies, especially immunotherapy, should take these dynamics of the immune response in RCC patients into account.

• Klíčová slova
• CTL, DC, Dendritic cells, NK, Neutrophils, PB, RCC, Regulatory T cells, Renal cell carcinoma, TIN, Treg, Tumor infiltration, cytotoxic T lymphocytes, dendritic cells, mDC, myeloid dendritic cells, natural killer, pDC, peripheral blood, plasmacytoid dendritic cells, regulatory T lymphocytes, renal cell carcinoma, tumor infiltrating neutrophils,
• MeSH
• aktivace lymfocytů imunologie   MeSH
• antigen CD83 MeSH
• antigeny CD45 metabolismus   MeSH
• CD antigeny metabolismus   MeSH
• dendritické buňky imunologie   MeSH
• dospělí MeSH
• imunoglobuliny metabolismus   MeSH
• karcinom z renálních buněk imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové glykoproteiny metabolismus   MeSH
• myeloidní buňky imunologie   MeSH
• nádorové mikroprostředí imunologie   MeSH
• nádory ledvin imunologie   MeSH
• neutrofily imunologie   MeSH
• počet lymfocytů MeSH
• regulační T-lymfocyty imunologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD45 MeSH
• CD antigeny MeSH
• imunoglobuliny MeSH
• membránové glykoproteiny MeSH
• PTPRC protein, human MeSH Prohlížeč

The tonsils are organized as lymphoepithelial structures that play an important role in protecting both the upper respiratory and alimentary tract regions against incoming antigens. This function requires dendritic cells, professional antigen-presenting cells that act as peripheral sentinels, specializing in the uptake, processing and presentation of antigenic material. This article gives a brief review on dendritic cells with regard to their origin, life cycle and functions in the pharyngeal mucosa. The regulation of immune responses in tonsils by dendritic cells is discussed. Their importance in some disease states is also mentioned.

• MeSH
• buněčná imunita imunologie   MeSH
• buněčný cyklus fyziologie   MeSH
• buněčný rodokmen fyziologie   MeSH
• dendritické buňky imunologie   fyziologie   MeSH
• farynx imunologie   fyziologie   MeSH
• histiocytóza z Langerhansových buněk imunologie   MeSH
• infekce imunologie   MeSH
• krční mandle imunologie   MeSH
• lidé MeSH
• nádory imunologie   MeSH
• respirační sliznice imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Dendritic cell (DC) therapy counts to the promising strategies how to weaken and eradicate cancer disease. We aimed to develop a good manufacturing practice (GMP) protocol for monocyte-derived DC (Mo-DC) maturation using circulating tumor cells lysates with subsequent experimental T-cell priming in vitro. METHODS: DC differentiation was induced from a population of immunomagnetically enriched CD14 + monocytes out of the leukapheresis samples (n = 6). The separation was provided automatically, in a closed bag system, using CliniMACS Prodigy® separation protocols (Miltenyi Biotec). For differentiation and maturation of CD14 + cells, DendriMACs® growing medium with supplements (GM-CSF, IL-4, IL-6, IL-1B, TNFa, PGE) was used. Immature Mo-DCs were loaded with autologous circulating tumor cell (CTCs) lysates. Autologous CTCs were sorted out by size-based filtration (MetaCell®) of the leukapheresis CD14-negative fraction. A mixture of mature Mo-DCs and autologous non-target blood cells (NTBCs) was co-cultured and the activation effect of mature Mo-DCs on T-cell activation was monitored by means of multimarker gene expression profiling. RESULTS: New protocols for mMo-DC production using automatization and CTC lysates were introduced including a feasible in vitro assay for mMo-DC efficacy evaluation. Gene expression analysis revealed elevation for following genes in NTBC (T cells) subset primed by mMo-DCs: CD8A, CD4, MKI67, MIF, TNFA, CD86, and CD80 (p ≤ 0.01). CONCLUSION: Summarizing the presented data, we might conclude mMo-DCs were generated using CliniMACS Prodigy® machine and CTC lysates in a homogenous manner showing a potential to generate NTBC activation in co-cultures. Identification of the activation signals in T-cell population by simple multimarker-qPCRs could fasten the process of effective mMo-DC production.

• Klíčová slova
• Circulating tumor cells, Dendritic cells, Immunotherapy, MetaCell, Personalized medicine, T cells,
• MeSH
• dendritické buňky * metabolismus   MeSH
• faktor stimulující granulocyto-makrofágové kolonie farmakologie   MeSH
• interleukin-4 farmakologie   MeSH
• interleukin-6 farmakologie   MeSH
• lidé MeSH
• monocyty * metabolismus   MeSH
• nádorové cirkulující buňky * metabolismus   MeSH
• prostaglandiny E farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• faktor stimulující granulocyto-makrofágové kolonie MeSH
• interleukin-4 MeSH
• interleukin-6 MeSH
• prostaglandiny E MeSH

Dendritic cells (DCs) are extremely efficient antigen-presenting cells that are potent stimulators of both B and T cell immune responses. Although DCs are normally present in extremely small numbers in the circulation, recent advances in DC biology have made it possible to generate DCs in culture. DCs can be generated in vitro from various cellular sources including bone marrow, cord blood and peripheral blood. Although culture conditions are extremely diverse, the majority of protocols grow DCs in GM-CSF and either TNF-alpha and/or IL-4. The addition of other growth factors such as SCF and Flt-3 ligand can dramatically enhance DC recovery. It is important to appreciate that DC subsets have been identified. Thus, DC at different stages of maturation, based on phenotype and capacity to capture antigen, can be obtained depending on culture conditions. For clinical applications, DCs can be generated in serum-free media and cryopreserved for future clinical applications. The ability to obtain DCs in numbers suitable for manipulating immune responses has pushed DC-based immunotherapies into the spotlight for treatment of various malignancies, including multiple myeloma, a B cell malignancy that is presently incurable. Although high-dose chemotherapy and transplantation have improved complete remission rates and overall survival in myeloma, immunotherapeutic strategies are needed for the additional cytoreduction needed to achieve a cure. Because DCs specialize in antigen capture and are extremely potent at stimulating T cell responses, they are ideally suited for generating anti-myeloma T cell responses in vivo. Several studies have demonstrated that myeloma protein, also called idiotype (Id), is sufficiently immunogenic and can be used to generate in vivo T cell responses in myeloma patients. Clinical trials using Id-pulsed DCs as a vaccine to treat minimal residual disease or relapsed myeloma are currently underway. Feasibility studies indicate that antigen-pulsed autologous DCs can be used to elicit in vivo Id-specific T cell responses. Additional studies are needed to optimize current DC vaccination protocols and determine clinical benefits associated with this approach. It is hoped that, following conventional therapies, a combination of adoptive immunotherapeutic modalities such as DCs together with myeloma-specific T cells may lead to improved clinical responses in multiple myeloma, and ultimately lead to complete remission and cure.

• MeSH
• buněčné kultury MeSH
• dendritické buňky imunologie   transplantace   MeSH
• imunoterapie * MeSH
• kryoprezervace MeSH
• kultivační média MeSH
• lidé MeSH
• mnohočetný myelom imunologie   terapie   MeSH
• T-lymfocyty imunologie   MeSH
• vakcinace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• kultivační média MeSH

This artide gives a brief review on dendritic cells (DC) with regard to their origin, life cyde and functions. The regulation of immune responses by DC functioning as antigen-presenting cells is discussed. Special attention is given to epidermal DC, e.g. Langerhans cells. The perspectives of DC-based therapy are also mentioned.

• MeSH
• buněčný cyklus imunologie   MeSH
• dendritické buňky imunologie   patologie   MeSH
• imunitní systém fyziologie   MeSH
• kůže imunologie   MeSH
• lidé MeSH
• senzitivita a specificita MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

COVID-19, caused by SARS-CoV-2 virus, emerged as a pandemic disease posing a severe threat to global health. To date, sporadic studies have demonstrated that innate immune mechanisms, specifically neutrophilia, NETosis, and neutrophil-associated cytokine responses, are involved in COVID-19 pathogenesis; however, our understanding of the exact nature of this aspect of host-pathogen interaction is limited. Here, we present a detailed dissection of the features and functional profiles of neutrophils, dendritic cells, and monocytes in COVID-19. We portray the crucial role of neutrophils as drivers of hyperinflammation associated with COVID-19 disease via the shift towards their immature forms, enhanced degranulation, cytokine production, and augmented interferon responses. We demonstrate the impaired functionality of COVID-19 dendritic cells and monocytes, particularly their low expression of maturation markers, increased PD-L1 levels, and their inability to upregulate phenotype upon stimulation. In summary, our work highlights important data that prompt further research, as therapeutic targeting of neutrophils and their associated products may hold the potential to reduce the severity of COVID-19.

• Klíčová slova
• COVID-19, IFN alpha, PD-L1, SARS-CoV-2, cytokine storm, degranulation, dendritic cells, innate immunity, monocytes, neutrophils,
• MeSH
• antigeny CD274 genetika   metabolismus   MeSH
• COVID-19 MeSH
• cytokiny genetika   metabolismus   MeSH
• dendritické buňky imunologie   MeSH
• dospělí MeSH
• imunofenotypizace MeSH
• koronavirové infekce krev   imunologie   MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• monocyty imunologie   MeSH
• neutrofily imunologie   MeSH
• pandemie MeSH
• přirozená imunita MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• virová pneumonie krev   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD274 MeSH
• CD274 protein, human MeSH Prohlížeč
• cytokiny MeSH

Dendritic cells (DCs) are key regulators of immune responses that operate at the interface between innate and adaptive immunity, and defects in DC functions contribute to the pathogenesis of a variety of disorders. For instance, cancer evolves in the context of limited DC activity, and some autoimmune diseases are initiated by DC-dependent antigen presentation. Thus, correcting aberrant DC functions stands out as a promising therapeutic paradigm for a variety of diseases, as demonstrated by an abundant preclinical and clinical literature accumulating over the past two decades. However, the therapeutic potential of DC-targeting approaches remains to be fully exploited in the clinic. Here, we discuss the unique features of DCs that underlie the high therapeutic potential of DC-targeting strategies and critically analyze the obstacles that have prevented the full realization of this promising paradigm.

• Klíčová slova
• autoimmune disorders, cancer, dendritic cells, immunotherapy, vaccine preparation,
• MeSH
• antigen prezentující buňky imunologie   metabolismus   MeSH
• autoimunita MeSH
• autoimunitní nemoci etiologie   metabolismus   terapie   MeSH
• buněčná diferenciace genetika   imunologie   MeSH
• dendritické buňky imunologie   metabolismus   MeSH
• imunita * MeSH
• imunologická tolerance * MeSH
• imunoterapie MeSH
• lidé MeSH
• mezibuněčná komunikace MeSH
• náchylnost k nemoci MeSH
• nádory etiologie   metabolismus   patologie   terapie   MeSH
• plasticita buňky genetika   imunologie   MeSH
• prezentace antigenu imunologie   MeSH
• protinádorové vakcíny aplikace a dávkování   imunologie   MeSH
• T-lymfocyty imunologie   metabolismus   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• protinádorové vakcíny MeSH

Dendritic cells form the connection between innate and adoptive mechanisms of the immune system. As antigen-presenting cells, dendritic cells are capable of presenting tumour antigen and effectively stimulating immune response targeted against a tumour. A number of preclinical and clinical studies document dendritic cells' potential in anti-cancer treatment. Increasing knowledge of dendritic cell biology is leading to improved methods for their preparation for clinical application. Unfortunately, there is to date no consensus specifying optimal conditions for dendritic cell preparation in vitro. This review summarizes the methods used for preparing myeloid dendritic cells derived from monocytic precursors while focusing on cytokine cocktails used for their growth, maturation, and functional adjustment.

• MeSH
• antigeny nádorové imunologie   MeSH
• buněčné kultury MeSH
• cytokiny imunologie   MeSH
• dendritické buňky imunologie   fyziologie   MeSH
• imunoterapie adoptivní metody   MeSH
• lidé MeSH
• monocyty imunologie   MeSH
• nádory terapie   MeSH
• T-lymfocyty imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antigeny nádorové MeSH
• cytokiny MeSH

Medullary thymic epithelial cells (mTECs), which produce and present self-antigens, are essential for the establishment of central tolerance. Since mTEC numbers are limited, their function is complemented by thymic dendritic cells (DCs), which transfer mTEC-produced self-antigens via cooperative antigen transfer (CAT). While CAT is required for effective T cell selection, many aspects remain enigmatic. Given the recently described heterogeneity of mTECs and DCs, it is unclear whether the antigen acquisition from a particular TEC subset is mediated by preferential pairing with a specific subset of DCs. Using several relevant Cre-based mouse models that control for the expression of fluorescent proteins, we have found that, in regards to CAT, each subset of thymic DCs preferentially targets a distinct mTEC subset(s). Importantly, XCR1+-activated DC subset represented the most potent subset in CAT. Interestingly, thymic DCs can also acquire antigens from more than one mTEC, and of these, monocyte-derived dendritic cells (moDCs) were determined to be the most efficient. moDCs also represented the most potent DC subset in the acquisition of antigen from other DCs. These findings suggest a preferential pairing model for the distribution of mTEC-derived antigens among distinct populations of thymic DCs.

• Klíčová slova
• cell biology, central tolerance, cooperative antigen transfer, dendritic cells, immunology, inflammation, mouse, thymic epithelial cells, thymus,
• MeSH
• autoantigeny metabolismus   MeSH
• dendritické buňky imunologie   metabolismus   MeSH
• epitelové buňky imunologie   metabolismus   MeSH
• imunologická tolerance * MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• prezentace antigenu imunologie   MeSH
• thymus cytologie   imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoantigeny MeSH