Search

[Display omitted] • The immune response and inflammation in pulmonary hypertension (PH) have been systematically summarized based on recent studies. • The relationship between CC chemokines and the pathogenesis of pH is summarized in clinical and animal models. • We found that although the immune response serves as an important potential factor in the pathogenesis of PH, less attention has been paid to CC chemokines and their receptors. • We believe that a greater understanding of the relationship between PH and CC chemokines and their receptors is a pressing issue. • We believe that we need to further clarify the pathogenesis of pH and provide basis for the clinical treatment of PH. Pulmonary hypertension (PH) represents a progressive condition characterized by the remodeling of pulmonary arteries, ultimately culminating in right heart failure and increased mortality rates. Substantial evidence has elucidated the pivotal role of perivascular inflammatory factors and immune dysregulation in the pathogenesis of PH. Chemokines, a class of small secreted proteins, exert precise control over immune cell recruitment and functionality, particularly with respect to their migration to sites of inflammation. Consequently, chemokines emerge as critical drivers facilitating immune cell infiltration into the pulmonary tissue during inflammatory responses. This review comprehensively examines the significant contributions of CC chemokines in the maintenance of immune cell homeostasis and their pivotal role in regulating inflammatory responses. The central focus of this discussion is directed towards elucidating the precise immunoregulatory actions of CC chemokines concerning various immune cell types, including neutrophils, monocytes, macrophages, lymphocytes, dendritic cells, mast cells, eosinophils, and basophils, particularly in the context of pH processes. Furthermore, this paper delves into an exploration of the underlying pathogenic mechanisms that underpin the development of PH. Specifically, it investigates processes such as cellular pyroptosis, examines the intricate crosstalk between bone morphogenetic protein receptor type 2 (BMPR2) mutations and the immune response, and sheds light on key signaling pathways involved in the inflammatory response. These aspects are deemed critical in enhancing our understanding of the complex pathophysiology of PH. Moreover, this review provides a comprehensive synthesis of findings from experimental investigations targeting immune cells and CC chemokines. Aim of review : In summary, the inquiry into the inflammatory responses mediated by CC chemokines and their corresponding receptors, and their potential in modulating immune reactions, holds promise as a prospective avenue for addressing PH. The potential inhibition of CC chemokines and their receptors stands as a viable strategy to attenuate the inflammatory cascade and ameliorate the pathological manifestations of PH. Nonetheless, it is essential to acknowledge the current state of clinical trials and the ensuing progress, which regrettably appears to be less than encouraging. Substantial hurdles exist in the successful translation of research findings into clinical applications. The intention is that such emphasis could potentially foster the advancement of potent therapeutic agents presently in the process of clinical evaluation. This, in turn, may further bolster the potential for effective management of PH. [ABSTRACT FROM AUTHOR]

Food allergy (FA) is an immune system reaction that occurs soon after eating certain food, which severely damages the health of allergic patients. Since medical approaches for FA may trigger severe adverse effects, the natural substances with anti-allergy functions have received more and more attention. This paper reviewed the natural bioactive substances with anti-allergic properties in food allergy, which mainly include polyphenols, polysaccharides, oligosaccharides, traditional Chinese medicine (TCM) and probiotics. Moreover, this paper analyzed the limitations of current investigations and provided future outlook for the development of anti-allergic products. This paper extensively reviews the natural substances with anti-allergy functions. As the results, the polyphenols could inhibit the formation of allergen-IgE complex, influence the allergen-IgE complex bind to the receptor (FcϵRI) on the surface of effector cells (e.g. mast cells and basophils). The polysaccharides and oligosaccharides could inhibit the secretion of allergic mediators and cytokines, suppressing Th2 responses and promoting Th1/Treg responses. The TCM could reduce allergen presentation to dendritic cell, weaken the secretion of allergen-specific IgE and the degranulation of mast cell, upregulate Th1 cytokines (e.g. IL-12, IFN-γ) and downregulate Th2 cytokines (e.g. IL-4, IL-13). The probiotics could help maintain the integrity of intestinal epithelial barriers by promoting mucus production via goblet cells, which could reduce the intestinal permeability and improved mucus generation to decrease the risk of food allergen into immune systems. This review could provide a better understanding and future outlook on the natural anti-allergy substances and supply a novel insight into their potential application for FA prevention and treatment. • Polyphenols, polysaccharides and probiotics are beneficial to alleviate food allergy. • Polyphenols could inhibit the IgE secretion and degranulation of effector cells. • Polysaccharides could inhibit the secretion of allergic mediators and cytokines. • Probiotics maintain intestinal epithelial barrier integrity and help prevent allergens. [ABSTRACT FROM AUTHOR]

Despite the global administration of approved COVID-19 vaccines (e.g., ChAdOx1 nCoV-19®, mRNA-1273®, BNT162b2®), the number of infections and fatalities continue to rise at an alarming rate because of the new variants such as Omicron and its subvariants. Including COVID-19 vaccines that are licensed for human use, most of the vaccines that are currently in clinical trials are administered via parenteral route. However, it has been proven that the parenteral vaccines do not induce localized immunity in the upper respiratory mucosal surface, and administration of the currently approved vaccines does not necessarily lead to sterilizing immunity. This further supports the necessity of a mucosal vaccine that blocks the main entrance route of COVID-19: nasal and oral mucosal surfaces. Understanding the mechanism of immune regulation of M cells and dendritic cells and targeting them can be another promising approach for the successful stimulation of the mucosal immune system. This paper reviews the basic mechanisms of the mucosal immunity elicited by mucosal vaccines and summarizes the practical aspects and challenges of nanotechnology-based vaccine platform development, as well as ligand hybrid nanoparticles as potentially effective target delivery agents for mucosal vaccines. This review shows the induction of mucosal immunity efficiently induces secretory IgA and IgG in the upper respiratory tract and systemic immunity via intranasal administration of nanovaccine. [Display omitted] [ABSTRACT FROM AUTHOR]

• Impulsive differential equations are used to capture the characteristics of intermittent androgen deprivation therapy. • The dynamics of tumours are sensitive to stochastic noise and tumour antigenicity. • The sufficient conditions for the existence of ergodic stationary distribution are established. • The results show that comprehensive therapy is more effective than a single therapy. Intermittent androgen deprivation therapy is one of the most commonly used therapeutic regimens for treating prostate cancer. Immunotherapy with dendritic cells, which act as the most robust antigen-presenting cells, are regarded as an effective method for the treatment of advanced prostate cancer. This paper utilizes impulsive differential equations to describe the combinations of a dendritic cell vaccine and intermittent androgen therapy with white noise. The tumour-free solution is obtained and the unique global positive solution of the system is explored. Then it is proved that the solutions of the system are stochastic ultimately bounded and stochastically permanent. In addition, threshold conditions for the extinction and persistence of prostate cancer cells are derived, and the stationary distribution and ergodicity of the system are investigated. Finally, numerical studies and the biological significance of the results are discussed. [ABSTRACT FROM AUTHOR]

Scheme 1. Schematic illustration of CRT valgus CT-26 tumor cell membranes-coated bacterial whole peptidoglycan (CPW/SR) combined with radiotherapy for cancer immunotherapy. (A) Preparation process of CPW/SR. (B) CPW/SR can activate the innate immunity by inducing DCs maturation, subsequently activate the adaptive immunity to play a role in cancer immunotherapy. [Display omitted] Immunotherapy has achieved some success in preclinical and clinical studies, but the immunosuppressive tumor microenvironment (TME) leads to a low response rate of this therapy. In this paper, we describe a calreticulin (CRT) valgus CT-26 tumor cell membranes-coated bacterial whole peptidoglycan (WPG) from P. aeruginosa (CPW/SR) with a high rate of the STING agonist loading. In the construct, WPG from P. aeruginosa (P.WPG) was used as a carrier with the immunoadjuvant function while synergistically promoting the maturation of dendritic cells (DCs) through the delivery of the STING agonist SR-717. CRT valgus tumor cell membranes were identified and internalized by DCs via CRT on the surface. In addition, this construct was able to reverse the immunosuppressive TME in vivo and achieve synergies with radiotherapy by creating a personalized tumor vaccine, therefore achieving more resultful antitumor efficacy. In conclusion, CPW/SR constructed in this paper provides a new approach for achieving efficient cancer immunotherapy and combination therapy. [ABSTRACT FROM AUTHOR]

• Release of Tumor-derived Exosomes (TDEs) is involved in intercellular information exchange. • Tumor-derived Exosomes (TDEs) can negatively regulate the tumor microenvironment. • Tumor-derived Exosomes (TDEs) inhibit peritumour immune cells and create an immunosuppressive environment. Tumor-derived exosomes (TDEs), as topologies of tumor cells, not only carry biological information from the mother, but also act as messengers for cellular communication. It has been demonstrated that TDEs play a key role in inducing an immunosuppressive tumor microenvironment (TME). They can reprogram immune cells indirectly or directly by delivering inhibitory proteins, cytokines, RNA and other substances. They not only inhibit the maturation and function of dendritic cells (DCs) and natural killer (NK) cells, but also remodel M2 macrophages and inhibit T cell infiltration to promote immunosuppression and create a favorable ecological niche for tumor growth, invasion and metastasis. Based on the specificity of TDEs, targeting TDEs has become a new strategy to monitor tumor progression and enhance treatment efficacy. This paper reviews the intricate molecular mechanisms underlying the immunosuppressive effects induced by TDEs to establish a theoretical foundation for cancer therapy. Additionally, the challenges of TDEs as a novel approach to tumor treatment are discussed. [ABSTRACT FROM AUTHOR]

Mucosal immunization is a powerful weapon against viral infection. In this paper, large pore mesoporous silica nanoparticles (LMSN) with different particle sizes were synthesized for loading influenza split vaccine (SV) to explore the effect of nanoparticle sizes on mucosal immunization and adjuvant efficacy. Interestingly, it was found that among the three particle sizes of nanoparticles, only LMSN-M with around 250 nm could significantly enhance the mucosal immune effect of SV, possessing adjuvant effect. The results indicated that particle size affected the adjuvant effect of LMSN. There was no apparent difference in vaccine loading capacity of LMSN with different particle sizes, but the release of SV depended on the pore length of LMSN. The adjuvant effect of LMSN-M was attributed to its higher cellular uptake performance, intestine absorption and transport efficiency, and the ability to stimulate the maturation of dendritic cells. Simultaneously, compared with LMSN-S and LMSN-L, the more retention of LMSN-M in mesenteric lymph nodes increased the chance of interaction between vaccine and immune system, resulting in the enhanced immunity. This is the first time to study the impact of particle size of LMSN adjuvant on improving mucosal immunity of oral influenza vaccine, and the present work provides a scientific reference for adjuvant design of oral vaccine. • LMSN with different small particle sizes for oral delivery of split vaccine. • The effect of nanoparticle size on mucosal immunization and adjuvant efficacy. • Reasons for different immunization effects caused by nanoparticle size was studied. • Providing a scientific reference for adjuvant design of oral vaccine. [ABSTRACT FROM AUTHOR]

• The electrochemical conversion of quinoxaline and 1,2,3,4-tetrahydroquinoxaline reached 90% and 100%, respectively. • The established hydrogen storage system exhibited excellent reversibility under mild conditions. • Dendritic P-WO 3 /NF was employed as an efficient dual-functional electrode. • The hydrogenation reaction was completed without an external hydrogen supply. Liquid organic hydrogen carrier (LOHC) has been recognized as a highly promising candidate for hydrogen storage materials in addressing hydrogen utilization issues. However, the hydrogenation and dehydrogenation of LOHC typically require noble metal catalysts and harsh reaction conditions. In this paper, we proposed an efficient reversible electrochemical hydrogen storage system based on a nitrogen heterocyclic organic hydrogen carrier, quinoxaline, in which water was used as the solvent and hydrogen source for quinoxaline hydrogenation, and a self-supporting dendritic P-WO 3 /NF electrode was employed as the electrocatalyst. The catalytic properties of P-WO 3 /NF for electrochemical hydrogenation of quinoxaline and dehydrogenation of 1,2,3,4-tetrahydroquinoxaline were studied in 1 M KOH solution under mild conditions. The results showed that the hydrogenation conversion of quinoxaline was 90%, the selectivity was 99%, and the dehydrogenation conversion of 1,2,3,4-tetrahydroquinoxaline was 100%, the selectivity was 100%. This indicates that the system has high conversion efficiency, outstanding selectivity, and good reversibility. Meanwhile, the P-WO 3 /NF electrode adapted to the system exhibited good catalytic stability. In addition, no pre-prepared external hydrogen was required in the electrochemical hydrogenation reaction involving water, which gave the system an excellent safety profile. The reversible electrochemical hydrogen storage system established by this work broadens the vision of LOHC in hydrogen storage applications. [Display omitted] [ABSTRACT FROM AUTHOR]

In a recent paper, Schriek et al. show that, in a complement-dependent reaction, marginal zone B cells (MZBs) steal MHC class II (MHCII) from dendritic cells (DCs). Activation of T cells by stolen MHCII complexes potentially allows MZBs to augment or regulate T cell activation in ways that are distinct from DCs. [ABSTRACT FROM AUTHOR]

Despite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal is the ultimate goal of kidney transplantation, and is made possible by the induction of immunological tolerance. The purpose of this paper is to review the safety and efficacy of immune tolerance induction strategies in living-donor kidney transplantation, both chimerism-based and non-chimerism-based. The impact of these strategies on transplant outcomes, including acute rejection, allograft function and survival, cost, and immune monitoring, will also be discussed. Databases such as PubMed, Scopus, and Web of Science, as well as additional online resources such as EBSCO, were exhaustively searched. Adult living-donor kidney transplant recipients who developed chimerism-based tolerance after concurrent bone marrow or hematopoietic stem cell transplantation or those who received non-chimerism-based, non-hematopoietic cell therapy using mesenchymal stromal cells, dendritic cells, or regulatory T cells were studied between 2000 and 2021. Individual sources of evidence were evaluated critically, and the strength of evidence and risk of bias for each outcome of the transplant tolerance study were assessed. From 28,173 citations, 245 studies were retrieved after suitable exclusion and duplicate removal. Of these, 22 studies (2 RCTs, 11 cohort studies, 6 case-control studies, and 3 case reports) explicitly related to both interventions (chimerism- and non-chimerism-based immune tolerance) were used in the final review process and were critically appraised. According to the findings, chimerism-based strategies fostered immunotolerance, allowing for the safe withdrawal of immunosuppressive medications. Cell-based therapy, on the other hand, frequently did not induce tolerance except for minimising immunosuppression. As a result, the rejection rates, renal allograft function, and survival rates could not be directly compared between these two groups. While chimerism-based tolerance protocols posed safety concerns due to myelosuppression, including infections and graft-versus-host disease, cell-based strategies lacked these adverse effects and were largely safe. There was a lack of direct comparisons between HLA-identical and HLA-disparate recipients, and the cost implications were not examined in several of the retrieved studies. Most studies reported successful immunosuppressive weaning lasting at least 3 years (ranging up to 11.4 years in some studies), particularly with chimerism-based therapy, while only a few investigators used immune surveillance techniques. The studies reviewed were often limited by selection, classification, ascertainment, performance, and attrition bias. This review demonstrates that chimerism-based hematopoietic strategies induce immune tolerance, and a substantial number of patients are successfully weaned off immunosuppression. Despite the risk of complications associated with myelosuppression. Non-chimerism-based, non-hematopoietic cell protocols, on the other hand, have been proven to facilitate immunosuppression minimization but seldom elicit immunological tolerance. However, the results of this review must be interpreted with caution because of the non-randomised study design, potential confounding, and small sample size of the included studies. Further validation and refinement of tolerogenic protocols in accordance with local practice preferences is also warranted, with an emphasis on patient selection, cost ramifications, and immunological surveillance based on reliable tolerance assays. • Chimerism- and non-chimerism-based immune tolerance strategies were reviewed in transplant recipients • Both strategies allowed for safe discontinuation of immunosuppressive medications with comparable rejection rates and allograft survival • The myelosuppression-related risk tended to be lower in non-chimerism-based tolerance regimens • Most studies reviewed were limited by small sample sizes, and only a few examined cost implications and immune surveillance techniques • Further validation of the tolerogenic protocols is warranted in large-scale studies [ABSTRACT FROM AUTHOR]

In this paper, the microstructure formation mechanism of an AlSi10Mg alloy prepared by laser directed energy deposition (DED-LB) and its influence on the mechanical properties was fully studied. The relationships between the microstructure characteristic scale, the molten pool solidification/thermal cycle conditions, and the tensile mechanical properties were established by combining the numerical simulation, theoretical calculation, and experimental validation. The as-deposited microstructure consists of the columnar α-Al dendritic array growing epitaxially along the building direction with the primary dendritic arm spacing of 18 ± 4.5 µm, the dendritic arm cell of 3 ± 1 µm surrounded by the refined eutectic network, and the Si precipitation of 17.7 ± 0.8 nm dispersed in the α-Al dendritic trunk. The feature size of the primary dendritic arm spacing and the dendritic arm cell size can be well predicted using the Kurz-Fisher and KGT dendritic growth models. The formation and size evolution of the Si precipitation was well described by the non-isothermal aging KWN model for the first time. The as-DED-LB-processed AlSi10Mg alloy exhibits a good comprehensive mechanical property with a yield strength of 187 ± 1.5 MPa and elongation to fracture of 7.4 ± 0.5%. The boundary strengthening from the eutectic phase network, the load-bearing capacity for dislocations caused by refined dendritic arms, and the precipitation strengthening of nano-Si particles play a major role in the improvement of the tensile strength and hardening ability. As a result, a quantitative relationship of the processing–microstructure–performance has been systematically investigated and established, which explores a method for the precision control and large-scale application of DED-AlSi10Mg alloys. [Display omitted] • Experiments and simulations of directed energy deposition AlSi10Mg parts. • Validity of theoretical solidification models on the microstructure. • Linking non-isothermal aging model to precipitated phase. • Quantitative relationships of processing–microstructure–performance. [ABSTRACT FROM AUTHOR]

Created with BioRender.com [Display omitted] Cancer immunity is dependent on dynamic interactions between T cells and dendritic cells (DCs). Polymer-based nanoparticles target DC receptors to improve anticancer immune responses. In this paper, DC surface receptors and their specific coupling natural ligands and antibodies are reviewed and compared. Moreover, reaction mechanisms are described, and the synergistic effects of immune adjuvants are demonstrated. Also, extracellular-targeting antigen-delivery strategies and intracellular stimulus responses are reviewed to promote the rational design of polymer delivery systems. [ABSTRACT FROM AUTHOR]

A numerically efficient 3D transient thermal-based computational framework was developed to predict the microstructure and morphology within the molten pool. The results show that a transition from curved cellular to columnar morphologies occurred while moving from the molten pool edge toward its tail, which was correlated with the ratio of local thermal gradient and the solidification rate. The higher cooling rates, at the melt pool center, are seem to favour the fine microstructure. The obtained cooling rates not only appeared to control the size of the microstructural grains but also the dendritic cell spacing within the melt pool. The microstructural features like dendrite cell spacing and the microhardness was predicted using the developed framework and validated within an error range of 7–12% and 4–6%, respectively. Moreover, a parametric study performed to investigate the effect of laser speed and power revealed that the microstructural variation was more sensitive to the scanning speed than to the input power of the simulated heat source. The obtained results from the developed numerical framework were validated with the experimentally observed values and are discussed in this paper. [Display omitted] • A FE-based framework to predict microstructural features has been developed. • Simulated thermal profile was coupled with the solidification curves of IN718. • The FE-results were validated successfully with CFD-based and experimental results. • High and low cooling rates implied finer and coarser microstructure, respectively. • The microstructural features were more sensitive to scanning speed than laser power. [ABSTRACT FROM AUTHOR]

• We systematically and in detail summarize the classification and biological characteristics of DC, as well as its development process. We focus on and deeply understand the role of DC in regulating the pathogenesis of different allergic diseases. • We demonstrate for the frist time the role of dendritic cells in various allergic diseases including AR, AA, AD, and FA. • Based on inflammatory response and immune regulation, a better understanding of the role of DC in immunomodulation and Th2 immune response can guide the development of new therapeutic targets for various allergic diseases and provide new ideas for the treatment of patients with allergic diseases. Allergic diseases are important diseases that affect many patients worldwide. Over the past few decades, the incidence of allergic diseases has increased significantly due to social development and increased environmental degradation, which has placed a huge economic burden on public health and even led to an increase in mortality. Substantial progress has been made in the understanding of the mechanisms of allergic diseases, and past studies have shown that the occurrence and development of allergic diseases are closely related to changes in the state of the immune system. With the study and in-depth understanding of innate immune lymphocytes, researchers have gradually discovered that dendritic cells (DC) play an important role in many allergic diseases. DC are the body's main antigen-presenting cells, which ingest, process, and hand allergens, and then secrete chemokines such as chemokine ligands 17(CCL17), CCL22, and upregulate their own surface co-stimulating molecules. Then DC present the antigen peptide to the initial T cells and further differentiate them into helper T cells 2(Th2). As an important part of humoral immunity, Th2 participates in the regulation of type 2 immune response through the secretion of cytokines such as interleukin 4(IL-4), IL-5, and IL-13 and plays a leading role. However, our current research on DC is limited and its status in allergic diseases is unclear.Among them, allergic rhinitis, allergic asthma, atopic dermatitis, and food allergy are DC-mediated Th2 immune-related factor disorder-related allergic diseases, and some progress has been made in recent years in the study of the pathogenesis of these diseases. This paper outlines the common phenotypes and activation pathways of DC in different allergic diseases as well as potential research directions to improve the understanding of its immunomodulatory role in different allergic diseases and ultimately find new ways to treat these diseases. [ABSTRACT FROM AUTHOR]

A failure of central immune tolerance driven by autoantigen specific T regulatory (Treg) cells is a major cause of many autoimmune diseases. Restoration of proper autoantigen Treg specific response holds promise as a highly effective, long-term therapy for a wide variety of autoimmune diseases. Generating autoantigen specific Tregs remains a challenge due to the non-specific nature of most tolerizing agents and the complexities of generating Tregs in vivo. Here we show a new push/pull method for inducing antigen-specific Treg tolerance via induction of tolerogenic dendritic cells (tolDCs). We identified a combination of three tolerogenic drugs, dexamethasone, simvastatin and SC-514, which when used in combination with toll-like-receptor (TLR) agonists induces an active tolDC phenotype. When the tolerogenic combination was packaged into a liposome with a model antigen such as ovalbumin (OVA), these tolDCs induce differentiation of OVA specific Tregs both ex vivo and in vivo. We examined the tolerizing potential of the combination in an experimental autoimmune encephalomyelitis (EAE) disease model. Given the antigen specificity of this technique, this paper presents an attractive preclinical autoimmune therapy. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) play a pivotal role in initiating antigen-specific tumor immunity. However, the abnormal function of DCs owing to the immunosuppressive tumor microenvironment (TME) and the insufficient number of tumor infiltrating DCs could promote immune tolerance and tumor immune escape. Thus, there is great potential to employ DCs to induce efficient antitumor immunity. In this paper, we developed intelligent DCs (iDCs), which consist of nanoparticles loaded with photothermal agents (IR-797) and coated with a mature DC membrane. The DC cell membrane on the surface of iDCs preserves the ability to present antigens and prime T cells. The iDCs can also enter the lymph node and stimulate T cells. The activated T cells reduced the expression of heat shock proteins (HSPs) in tumor cells, rendering them more sensitive to heat stress. Subsequently, we used mild photothermal therapy (42–45 °C) to induce immunogenic cell death and contribute to a synergistic antitumor effect. iDCs as a refined and precise system in combination with DC-based immunotherapy and thermal therapy can be stored long-term and on a large scale, so they can be applied in many patients. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are the dominant class of antigen-presenting cells in humans; therefore, a range of DC-based approaches have been established to promote an immune response against cancer cells. The efficacy of DC-based immunotherapeutic approaches is markedly affected by the immunosuppressive factors related to the tumor microenvironment, such as adenosine. In this paper, based on immunological theories and experimental data, a hybrid model is designed that offers some insights into the effects of DC-based immunotherapy combined with adenosine inhibition. The model combines an individual-based model for describing tumor-immune system interactions with a set of ordinary differential equations for adenosine modeling. Computational simulations of the proposed model clarify the conditions for the onset of a successful immune response against cancer cells. Global and local sensitivity analysis of the model highlights the importance of adenosine blockage for strengthening effector cells. The model is used to determine the most effective suppressive mechanism caused by adenosine, proper vaccination time, and the appropriate time interval between injections. [Display omitted] • We propose a hybrid model to describe the immunosuppressive function of adenosine in tumor micro environment. • Our model provides immunologists with a new level of insight into the role of immunosuppressive factors of the immune system. • Our model highlights the importance of adenosine blockage for strengthening effector cells and suppressing Treg cells. • Model simulations are compatible with in vivo experimental data. • The results reveals that the appropriate time interval for administration of adenosine inhibitor is between 2 and 4 days. [ABSTRACT FROM AUTHOR]

• The phenotype of human CD303+ pDC subsets is investigated in this paper. Four new subpopulations of CD303 pDCs expressing CD205 and/or CD103 are found in human peripheral blood. • Non-small-cell lung cancer (NSCLC) modulates the differentiation of CD303+ pDC subsets expressing CD103 and CD205 in vitro and ex vivo. • Co-culture with primary NSCLC cells or NSCLC cell line (H1299) in vitro leads to abnormal expression of co-stimulatory molecules/MHC II (CD40, CD80, CD86 and HLA-DR) and production of pro-/anti-inflammatory cytokines (IL-6, IL-10, IL-12, IL-23, IL-27 and TGF-β) by CD303+ pDCs. • Our data indicated that NSCLC cells generate immune tolerogenic CD303+ pDC subsets in vitro. This may be one part of immune suppressive microenvironment induced by NSCLC in vivo. CD303+ plasmacytoid dendritic cells (pDCs) play an important role in the induction of immune tolerance and antitumor immunity. Here, we focused on the effect of NSCLC cells on the development of CD303+ pDC subsets expressing CD205 and/or CD103. The NSCLC cell line H1299 and primary NSCLC cells were incubated with DCs. The protein expression of costimulatory molecules on CD303+ pDCs, the production of pro-inflammatory and anti-inflammatory cytokines by CD303+ pDCs and the development of CD303+ pDC subsets were detected by using flow cytometry. Coculture with NSCLC cells modulates the protein expression of CD86 and HLA-DR on CD303+ pDCs. Moreover, NSCLC cells suppressed the production of IL-12 and IL-23 but facilitated the secretion of IL-27 and TGF-β by CD303+ pDCs. There were new CD303+ pDC subsets expressing CD205 and/or CD103 in healthy donors and NSCLC patients: CD303+CD205+CD103+, CD303+CD205+CD103-, CD303+CD205-CD103+ and CD303+CD205-CD103- pDCs. NSCLC cells modulated the differentiation of CD303+ pDC subpopulations by regulating the protein expression of CD205 and/or CD103 on CD303+ pDCs. NSCLC cells may regulate the immune functions of CD303+ pDCs by modulating the expression of costimulatory molecules on DCs and the production of pro-inflammatory/anti-inflammatory cytokines by DCs. NSCLC cells also regulate the development of CD303+ pDC subsets expressing CD205 and/or CD103. These outcomes may reveal a new cellular mechanism leading to the NSCLC-induced immune-suppressive microenvironment. [ABSTRACT FROM AUTHOR]