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Introduction. The mechanism of action of extracorporeal photopheresis (ECP) is associated with the induction of apoptosis of lymphocytes, which cause the activation of antigen-presenting cells (APC). As a result of the use of ECF, the number of T-regulatory lymphocytes increases, which induces an immunosuppressive effect. The actual problem lies in the use of cryopreserved and photo-irradiated mononuclear cells.Aim — to analyze the functional features of cryopreserved mononuclear cells after ECP.Materials and methods. The study analyzed the indicators of early and late stages of apoptosis in the concentrate of mononuclear cells of different groups, depending on the time of collection and the type of exposure on these concentrates of mononuclear cells: immediately after apheresis (groups 1.1 and 1.2), and after ECP (groups 1.3, 2.1 and 2.2), groups 1.2 and 2.2 were after cryopreservation, and 1.3 — after cryopreservation, and then after ECP. 113 samples of mononuclear cell concentrates obtained from 12 patients with chronic graft-versus-host reaction (GVHD) were analyzed. All groups of samples were cultured to determine the dynamics of changes in indicators of early and late stages of apoptosis over time.Results. The proportion of lymphocytes in the late stage of apoptosis after 2 days cultivation, after the standard ECP procedure, was comparable to the proportion of lymphocytes in the late stage of apoptosis during ECP followed by cryopreservation of the leukoconcentrate.Conclusion. It is advisable to collect mononuclear cells, perform their extracorporeal photo-irradiation, and then divide the photo-irradiated mononuclear cells into several parts both for cryopreservation and for the return of non-cryopreserved photo-irradiated mononuclear cells to the patient.

The abscopal effect has been mentioned since 1953. The increase in knowledge about the immune system and the development of immunotherapies support its potential therapeutic interest. While it is accepted that radiotherapy induces an immune response, demonstrating its systemic impact is not easy. The preclinical basis is solid but its clinical validation pending. Radiotherapy rarely induces tumor reduction at a distance from the beams, probably due to its immunosuppressive effect. This is why a synergy between radiotherapy and systemic treatments targeting these immunosuppressive mechanisms was observed. Several parameters can modulate the induction of the abscopal effect. Among these, the fractionation of the dose seems to be determining with currently a pre-eminence of hypofractionated stereotaxis. On the other hand, even if the choice of more immunogenic targets (liver, lung) should be favoured, the optimal number of lesions to be irradiated remains to be defined as well as the minimum volume allowing sufficient release of tumor antigens. The impact of radiation-induced lymphopenia on radiotherapy/immunotherapy efficacy needs to be assessed more precisely, as does the effect of radiotherapy techniques on them. Finally, the choice of immunotherapy(ies) and the combination regimen with radiotherapy remain under discussion. A sequential scheme appears to provide less toxicities but the concomitant would lead to a better response. The study of these different parameters should allow us to deliver optimized radiotherapy/immunotherapy(ies) combinations to our metastatic patients in order to benefit as many people as possible from this abscopal effect.

Various stresses (high temperature, starvation, or sublethal Cryptococcal infection) increased the susceptibility of silkworms to bacterial infection by up to 100-fold, confirming the stress-induced immunosuppression reported in a range of species. When the silkworm was injected with a steroidal drug, betamethasone (1 mg/larva), the susceptibility of the silkworm to bacterial infection increased about 100-fold. This indicates that the immune function of the silkworm can be suppressed by a known compound that shows immunosuppressive effects in humans. We further tested the immunosuppressive effect of the culture supernatants (acetone extracts) of soil bacteria, and 24 out of 193 isolates showed the immunosuppressive activity. These results suggest that it is possible to search for immunosuppressive agents targeting innate immunity by using a silkworm bacterial infection model as a screening system, and that there may be candidate compounds for immunosuppressive agents among the substances produced by soil bacteria.

Cyclophosphamide is one of the standard therapies for lupus, especially lupus nephritis based on its immunosuppressive effect. However, cyclophosphamide is also known as a nephrotoxic agent. Therefore, this research was aimed to measure the effect of cyclophosphamide at the dose that comparable to the human dose of 1 mg/kg BW on the kidney of lupus mice induced by means of 2,6,10,14-tetramethylpentadecane (TMPD). In this research, the IL-6 as a pro-inflammatory cytokine was tested by using flow cytometry method. In addition, the structural damage of the kidney tissues was assessed by means of Moroni’s kidney organ scoring method for lupus. The result showed that cyclophosphamide reduced the IL-6 significantly with the value of 36.72±22.79% for the TMPD-treated group; 32.59±9.97% for the cyclophosphamide group; and 30.25±4.48% for the naïve group. Moreover, the damages of the kidney tissues on the cyclophosphamide group were more severe than the TMPD-treated group. In conclusion, despite its anti-inflammatory effect which is useful for lupus, cyclophosphamide has a severe nephrotoxic effect which harms the patient. The effects may be a cause of the long interval use of cyclophosphamide. It can be a consideration for the further research and the next revision of the guideline for lupus nephritis treatment.

Összefoglaló. A COVID–19 mortalitását a súlyos társbetegségek, közöttük bizonyos daganatos betegségek is növelik. Immunszuppresszív hatásuk miatt felmerülhet a citotoxikus kezelések rizikónövelő hatása is. Ugyanakkor az onkológiai terápia megszakítása vagy halasztása, különösen az agresszívebb, kiterjedtebb és fiatalkorban jelentkező daganatok esetében ronthatja a kórjóslatot. Egy 39 éves nőbeteg esetét ismertetjük. A járvány során késlekedve felismert, lokoregionálisan kiterjedt emlődaganat miatt primer szisztémás kemoterápiában részesült. A kezelés 5. ciklusa során enyhe légúti tünetek kapcsán, az onkológiai ambulancián SARS-CoV-2-fertőzése igazolódott. Kemoterápiás kezelését felfüggesztettük. A diagnózistól számított 3. napon tünetmentessé vált, ám SARS-CoV-2-PCR-pozitivitása még a 43. napon is fennállt. A 19. napon hormongátló kezelést indítottunk. Az 51. napon mastectomia és axillaris block dissectio történt. A 82. napon a megszakított kemoterápiát a hormongátló kezelés leállítását követően G-CSF-profilaxis mellett újraindítottuk. A kezelés során fertőzéses szövődményt nem észleltünk. Kemoterápia és műtét SARS-CoV-2-fertőzött, tünetmentes daganatos betegnél szövődménymentesen végezhető elhúzódó virológiai pozitivitás esetén, felszabadító vizsgálat nélkül is. A daganatos betegek koronavírus-fertőzése esetén az onkológiai protokolltól történő eltérés egyénre szabott optimalizálásával és a multidiszciplináris team szorosabb együttműködésével az infektológiai és az onkológiai kockázat együttes alacsonyan tartása is megvalósítható. Orv Hetil. 2021; 162(16): 611–614. Summary. Mortality of COVID-19 is increased when certain co-morbidities, among others advanced malignancies are present. Deleterious effect of cytotoxic therapy, related to its immunosuppressive effect, may also be hypothesised. However, postponing or cancelling oncologic treatment, especially in younger patients with advanced and more aggressive tumors may worsen the prognosis. The case of a 39-year-old female patient is presented, who was diagnosed with loco-regionally advanced breast cancer during the pandemic. Primary systemic chemotherapy was started. The patient presented with acute respiratory tract symptoms during the fifth cycle and subsequently SARS-CoV-2 infection was diagnosed. Chemotherapy was cancelled. Symptoms resolved in three days after diagnosis. SARS-CoV-2 PCR remained positive up to day 43. Antihormonal therapy was introduced on day 19 and she underwent mastectomy with axillary lymph node dissection on day 51. Chemotherapy was reset postoperatively on day 82 with prophylactic G-CSF protection. No adverse event was observed throughout the treatment. Cytotoxic chemotherapy and surgery can be successfully delivered in breast cancer patients with prolonged asymptomatic SARS-CoV-2 PCR positivity, even without negative swab result. Individual optimisation of the therapy may require deviations from standard protocols. Closer multidisciplinary cooperation may contribute to the minimisation of both oncologic and infectious risks. Orv Hetil. 2021; 162(16): 611–614.

Cyclophosphamide (CYC) is an alkylating agent with immunosuppressive effect by inhibiting DNA synthesis and producing apoptosis used in many autoimmune diseases, including multiple sclerosis (MS). Here, we analyze the efficacy of CYC treatment in relapsing-remitting (RRMS) and active secondary progressive MS (SPMS) in our center with a monthly scheme. Patients with MS treated with CYC and a follow up of at least 36 months were eligible for inclusion. All participants had received a standard CYC regimen. The EDSS score mean annualized relapse rate (ARR) and progression index (PI) were measured as efficacy outcomes at 12, 24, and 36 months. Outcomes were also analyzed comparing disease course and activity. A total of 16 patients were included (50% male, 18.75% RRMS and 81.25% SPMS). EDSS remained stable along the follow-up period, with 62.5% improving or maintaining the same EDSS score at 12 months. PI decreased 14% and 21% at 12 and 24–36 months of follow-up, respectively. ARR decreased 20% after 12 months, 19% after 24 months, and 30.23% after 36 months. Median differences in ARR were higher in patients with high relapse activity (0.60 vs 0.07, p = 0.001) and malignant course (0.60 vs 0.17, p = 0.027). PI also differed with higher mean differences in patients with high relapse activity (0.70 vs 0.03, p = 0.016) and malignant course (1.17 vs 0.03, p = 0.003). CYC continues to be a valid therapeutic option, especially in regions with limited access to high-efficiency therapies particularly in patients with high relapsing activity and malignant course.

Cancer immunotherapy has veered the paradigm of cancer treatment. Despite recent advances in immunotherapy for improved antitumor efficacy, the complicated tumor microenvironment (TME) is highly immunosuppressive, yielding both astounding and unsatisfactory clinical successes. In this regard, clinical outcomes of currently available immunotherapy are confined to the varied immune systems owing in large part to the lack of understanding of the complexity and diversity of the immune context of the TME. Various advanced designs of nanomedicines could still not fully surmount the delivery barriers of the TME. The immunosuppressive TME may even dampen the efficacy of antitumor immunity. Recently, some nanotechnology-related strategies have been inaugurated to modulate the immunosuppressive cells within the tumor immune microenvironment (TIME) for robust immunotherapeutic responses. In this review, we will highlight the current understanding of the immunosuppressive TIME and identify disparate subclasses of TIME that possess an impact on immunotherapy, especially those unique classes associated with the immunosuppressive effect. The immunoregulatory cell types inside the immunosuppressive TIME will be delineated along with the existing and potential approaches for immunosuppressive cell modulation. After introducing the various strategies, we will ultimately outline both the novel therapeutic targets and the potential issues that affect the efficacy of TIME-based nanomedicines., Graphical abstract Immunosuppressive cells in the tumor immune microenvironment (TIME) are potential targets for nanomedicine-based immunotherapy. Various regulation strategies have been harnessed to modulate the immunosuppressive TIME.Image 1, Highlights • Immunosuppressive tumor microenvironment dampens the efficacy of antitumor immunity. • Immunosuppressive cells in the tumor microenvironment are responsible for the negative regulation of immune responses. • TAMs, MDSCs, Treg cells, and CAFs are the main immunosuppressive cells with extensive research. • Nanomedicines remodel the TIME by sensitizing the immunosuppressive cells and facilitating the immune cell recruitment. • Combined nanomedicine-based immunotherapy interacts with the cancer–immunity cycle, yielding amplified therapeutic effect.

Indoleamine 2,3-dioxygenase (IDO) is one of the initial rate-limiting enzymes of the kynurenine pathway (KP), which causes immune suppression and induction of T cell anergy. It is associated with the imbalance of immune homeostasis in numerous diseases including cancer, chronic viral infection, allergy, and autoimmune diseases. Recently, IDO has extended its role to liver field. In this review, we summarize the dysregulation and potentials of IDO in the emerging field of liver injuries, as well as current challenges for IDO targets. In particular, we discuss unexpected conclusions against previous work published. IDO is induced by pro-inflammatory cytokines in liver dysfunction and exerts an immunosuppressive effect, whereas the improvement of liver injury may require consideration of multiple factors besides IDO.

A thirty-eight-year-old uncontrolled diabetic with a recent COVID-19 infection presented with extensive bowel ischemia and gangrene with a microscopic diagnosis of intestinal and mesenteric mucormycosis. Although there are a few reported cases of primary gastrointestinal mucormycosis, our case showing involvement of the intestine and/or mesentery, that too in a post-COVID patient, is quite uncommon. The immunosuppressive effect of the COVID-19 disease, uncontrolled diabetes, and the use of corticosteroids for the treatment of severe COVID are the most probable reasons for the emergence of severe opportunistic infections, both as a coinfection and as a sequalae to COVID.

The aim of this work was to investigate the effect of Ochratoxin A (OTA) and Silymarin on serum lysozyme concentrations, complement and betalysin activity in broiler chickens. In this experiment 144 one-day-old Ross 308 male broiler chicks were used. All chicks were divided in four groups of 36 birds each: Group 1: Basal diet (BD) with no supplementation of Ochratoxin A (OTA) and Silymarin; Group 2: BD with 1.0% Silymarin; Group 3: BD with 3.0 mg/kg OTA; Group 4: BD with 3.0 mg/kg OTA plus 1.0% Silymarin. It was found that lysozyme concentration in the 2nd group there is a significant difference to groups 3 and 4. The immunosuppressive effect of Ochratoxin A is underlined but no protective effect of Silymarin in the group 4 was found. The alternative pathway of complement activation (APCA) is affected in the group 4. Betalysine there is a significant decreasing in the group 3 but slightly increasing of Betalysine in 4th group. Based on these results it can be concluded that OTA there is an immunosuppressive effect on the studied traits and there is a positive effect of Silymarin only on serum betalysine.

Background Over 20 kinds of steroids, tacrolimus ointments, and cyclosporine capsules are usually recommended for the treatment of atopic dermatitis (AD), depending on the symptoms of patients. However, several side effects sometimes occur with the extensive use of these agents for the treatment of pediatric AD patients. The purpose of this study was to explore whether vitamin K2 could be a new immunosuppressive candidate for pediatric patients with AD. Methods The immunosuppressive efficacy of vitamin K2 was evaluated through a cell-culture procedure using mitogen-activated peripheral blood mononuclear cells (PBMCs) obtained from pediatric AD patients. Results The mean (SD) IC50 value of vitamin K2 for the proliferation of concanavalin A-activated PBMCs was 15.37 (30.05) μmol/L, while the value for tacrolimus was 0.10 (0.28) ng/mL (0.12 (0.35) nmol/L). There was a significant correlation between the IC50 values for vitamin K2 and those for tacrolimus (P = 0.0001, r = 0.8871). However, there was no significant correlation between the IC50 values of vitamin K2 and those of cyclosporine A or methylprednisolone. A significant correlation between the IC50 values of vitamin K2 or tacrolimus and blood eosinophil counts (P = 0.0099, r = 0.7086 and P = 0.0032, r = 0.7722, respectively) was observed. Conclusion Vitamin K2 -inhibited T-cell mitogen stimulated proliferation of PBMCs from pediatric AD patients in a dose-dependent manner. The PBMCs from pediatric AD patients were more sensitive to the immunosuppressive efficacy of vitamin K2 than the PBMCs from healthy subjects. The individual immunosuppressive pharmacological efficacy of vitamin K2 and of tacrolimus could be inferred from the blood eosinophil count of pediatric AD patients.

Background and objectives The exosomes released by mesenchymal stromal cells (MSCs) in classical FBS-containing media have been demonstrated as an alternative, cell-free therapy in various diseases including inflammatory bowel disease (IBD). It has been found that the function of exosomes is affected by culture condition. We previously developed a serum-free, xeno-free and chemically defined medium, and umbilical cord-derived MSCs in this medium retained the immunosuppressive capability. Methods In this study, we evaluated the immunosuppressive function of exosomes from MSCs (MSC-Exo) in defined medium and their therapeutic effect on treating colitis. Results and conclusions In vitro studies indicated that MSC-Exo reduced the concentration of pro-inflammatory cytokines IFN-γ, TNF-α and IL-1β, and increased the secretion of anti-inflammatory cytokines TGF-β1 and IL-10, but no significant change of inhibitory effect on peripheral blood mononuclear cells proliferation was shown. In vivo experimental colitis showed that administration of MSC-Exo was able to significantly ameliorate the disease activity index score, weight loss, colon shortening, and the histological colitis score through up-regulation anti-inflammatory responses and down-regulation of inflammatory responses. Moreover, the use of MSC-Exo (200 µg) led to an improved therapeutic efficacy when compared with MSCs at a dose of 1×106 cells. Our findings indicate that the exosomes from MSCs in defined medium possess a certain degree of immunosuppressive effect in vitro and exhibit a therapeutic capability in a mouse model of DSS-induced colitis through suppressing inflammation mechanism.

Introduction. The pathological body response to metal implants is considered to be well known. There are a lot of studies devoted to this issue. This work is devoted to investigating the dynamic changes of haematological indicators as markers reflecting body response to the insertion of steel implants with diamond-carbon coating in rats. The purpose of the study is to assess the effects caused by steel implant with a diamond-coated coating on rat’s body by assessing hematological parameters. Materials and methods. The study involved 61 male rats: five of which were intact animals, and the rest was divided into two groups (28 animals in each). The first group was the control group, in which rats were inserted non-coated steel implants into the femoral metaphysic; the second group was test group, in which rats were inserted steel diamond-coated implants). The age of animals at the beginning of the experiment was 5–6 months, the body weight was 300–400 g. Blood for research was taken from the animals after decapitation in 7, 14, 30 and 90 days following the implantation. The blood samples were measured for the red blood cell, white blood cells, haemoglobin, leukogram. The findings obtained were processed by statistical analysis methods. Results and conclusions. The first group of the rats with inserted steel implants without coating showed the number of erythrocytes and haemoglobin did not differ from those in the intact rats, the leukocyte count on the 7th and 14th days was reduced by 31.8 % to 39.4 %, respectively; on the 7th day the percentage of lymphocytes and monocytes increased by 13.0 % and 5.0 % due to the toxic immunosuppressive effect of steel implants on the body of the experimental animals. The 2nd group of rats, which were inserted diamond-coated steel implants in their femurs, the rates of erythrocytopoiesis, the leukocyte number and leukogram characteristics remained unchanged during all the observation periods, except for an increase in the percentage of eosinophils on the 7th day and lymphocytes on the 90th day of follow- by 3 % that indicates a less pronounced body response in comparison with the animals of I group.

Betsch and Sprengholz (1) address the issue of supposedly increased severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) testing frequency in allergic patients during the pollen season because of the misinterpreted similar symptoms of allergic and viral rhinitis. We (2) had previously reported a significant and positive relationship between SARS-CoV-2 infections and airborne pollen concentrations in early Spring 2020, with potential mechanism of a previously discovered immunosuppressive effect of pollen on the nasal epithelium (3), possibly more pronounced in allergics due to a known intrinsic reduction of antiviral type I and type III interferon responses (4, 5). In this study (1), several parameters may have influenced the conclusion drawn. First, “allergic” participants were identified based on self-reported “hay fever” (yes/no) without further stratification for the type of pollen allergy; it … [↵][1]1To whom correspondence may be addressed. Email: thanos.damialis{at}tum.de. [1]: #xref-corresp-1-1

Background: In peripheral blood, human natural killer (NK) cells are immunological cells that nearly don’t express the ectonucleotidase CD73 on their plasma membrane. When exposed to mesenchymal stem cells (MSCs), NK cells are able to acquire CD73. MSCs are known to be CD73-positive (CD73+) and also to modulate the immune system, e.g. through adenosynergic pathway by ectonucleosidases, such as CD73. Extracellular vesicles (EVs) are involved in cell-to-cell communication. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as paracrine mediators that are part of MSC immunomodulatory effects including immunosuppressive properties and immune privilege. Objective: The aim of our work was to study if CD73 could be acquired by NK cells through cell-to-cell communication with MSC-EVs as cell culture additives. We also hypothesised that MSC-EVs would act as tolerance inducers to attenuate NK cell cytotoxicity. Methods: Cell isolation was made from human umbilical cords for MSCs and from human peripheral blood for NK cells. MSC-EVs were isolated by ultracentrifugation and filtration, then characterized by nanoparticle tracking assay and flow cytometry (CD9, 63, 81 and 73). MSC-EV interaction with NK cells was monitored by PKH67 staining. NK cell activation was followed by measuring the expression of CD73 and NK-activating receptor natural-killer group 2, member D (NKG2D) by flow cytometry. The cytotoxicity of NK cells or EV-conditioned NK cells was evaluated after co-culture with K562 cells. Results: We showed that MSC-EVs are nanoparticles able to express CD73 and interact with NK cells. MSC-EV conditioned NK cells seem to increase CD73 and decrease NKG2D through an EV-mediated mechanism. MSC-EVs have an immunosuppressive effect on NK cells by preventing NK cell activation and NK cell cytotoxicity towards K562 cells. Conclusions: Our results demonstrate that MSC-EVs could influence NK cell behaviour and act as immunosuppressant cell-based products.

Tumor xenograft models can create a high capacity to study human tumors and discover efficient therapeutic approaches. Here, we aimed to develop the gamma-radiated immunosuppressed (GIS) mice as a new kind of tumor xenograft model for biomedical studies. First, 144 mice were divided into the control and treated groups exposed by a medical Cobalt-60 apparatus in 3, 4, and 5 Gy based on the system outputs. Then, 144 BALB/c mice were divided into four groups; healthy, xenograft, radiation, and radiation + xenograft groups. The animals in the xenograft and radiation + xenograft groups have subcutaneously received 3 × 106 MCF-7 cells 24 h post-radiation. On 3, 7, 14, and 21 days after cell injection, the animals were sacrificed. Then, the blood samples and the spleen and tumor tissues were removed for the cellular and molecular analyses. The whole-body gamma radiation had a high immunosuppressive effect on the BALB/c mice from 1 to 21 days post-radiation. The macroscopic and histopathological observations have proved that the created clusters' tumor structure resulted in the xenograft breast tumor. There was a significant increase in tumor size after cell injection until the end of the study. Except for Treg, the spleen level of CD4, CD8, CD19, and Ly6G was significantly decreased in Xen + Rad compared to the Xen alone group on 3 and 7 days. Unlike IL-4 and IL-10, the spleen level of TGF-β, INF-γ, IL-12, and IL-17 was considerably decreased in the Xen + Rad than the Xen alone group on 3 and 7 days. The spleen expressions of the VEGF, Ki67, and Bax/Bcl-2 ratio were dramatically increased in the Xen + Rad group compared to the Xen alone on 3, 7, 14, and 21 days. Our results could confirm a new tumor xenograft model via an efficient immune-suppressive potential of the whole-body gamma radiation in mice.

Catgut implantation at acupoints (CIA) has a long history as a medical treatment for a wide variety of diseases, including autoimmune diseases. However, the effect and mechanism of this therapy in autoimmune uveitis is still largely unknown. The aim of this study was to explore the immunity-inhibitory effect of CIA in an experimental autoimmune uveitis (EAU) rat model. EAU was established in Lewis rats by the injection of IRBP1177–1191 peptide. The rats were randomly divided into control and CIA groups. Phenotypic and histological assessments were performed days 9, 13, 18, 23 post-immunization. The percentage of Th1 and Th17 lymphocytes isolated from lymph nodes were determined by flow cytometry. The expression of IL-17 and IFN-γ was detected by real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA). In the CIA group, delayed mild inflammation was observed. Pathological investigation found alleviated infiltration of lymphocytes and ocular damage. Flow cytometry showed significantly decreased Th17 lymphocytes at day 9, 13, and 18 post-immunization (P

Canine atopic dermatitis (CAD) is a chronic inflammatory skin disease and has a high frequency among dermatological diseases. The interaction of genetic factors, skin and environmental conditions affect the expression of the disease, developing a complex pathology. Current multimodal treatment has numerous adverse effects and variations in its efficacy and safety, demonstrating the need to develop safe and effective therapeutic resources for patients with CAD. Mesenchymal stem cells (MSCs) are multipotent cells, with special characteristics, such as self-renewal, immunomodulatory properties, and de-differentiation, making them useful for several clinical problems. The discovery of the immunosuppressive effect of MSCs on T cells has opened the potential for new perspectives with its use as a therapeutic agent for immune diseases, such as CAD. The scarce number of research using the MSC as a treatment for CAD result in the lack of knowledge about the benefits and possible protocols to be followed for the use of this cell therapy. In this review, we highlighted the clinical studies and potential biological mechanisms of MSC-based cell therapy effects attenuating canine atopic dermatitis compared to conventional treatment, which might lead to a safe improvement of the animal’s clinical condition in a short period without causing adverse effects.

The 16th Meeting of the Interuniversity Institute of Myology (IIM), October 17-20, 2019, Assisi, Italy brought together scientists, pharma and patient organization representatives discussing new results on muscle research. Internationally renowned Keynote speakers presented advances on muscle development, homeostasis, metabolism, and disease. Speakers selected among submitted abstracts presented their new, unpublished data in seven scientific sessions. The remaining abstracts were showcased in two poster sessions. Young trainees where directly involved in the selection of keynote speakers, the organizing scientific sessions and roundtables discussions tailored to the interests of their peers. A broad Italian, European and North-American audience participated to the different initiatives. The meeting allowed muscle biology researchers to discuss ideas and scientific collaborations aimed at better understanding the mechanisms underlaying muscle diseases in order to develop better therapeutic strategies. The active participation of young trainees was facilitated by the friendly and inclusive atmosphere, which fostered lively discussions identifying emerging areas of myology research and stimulated scientific cross-fertilization. The meeting was a success and the IIM community will continue to bring forward significant contributions to the understanding of muscle development and function, the pathogenesis of muscular diseases and the development of novel therapeutic approaches. Here, we report abstracts of the meeting illustrating novel results of basic, translational, and clinical research, which confirms that the Myology field is strong and healthy.

Myeloid-derived suppressor cells (MDSCs) are major immunosuppressive cells in the tumor microenvironment (TME). During the differentiation and development of MDSCs from myeloid progenitor cells, their functions are also affected by a series of regulatory factors in the TME, such as metabolic reprogramming, epigenetic modification, and cell signaling pathways. Additionally, there is a crosstalk between these regulatory factors. This review mainly introduces the metabolism (especially glucose metabolism) and significant epigenetic modification of MDSCs in the TME, and briefly introduces the connections between metabolism and epigenetic modification in MDSCs, in order to determine the further impact on the immunosuppressive effect of MDSCs, so as to serve as a more effective target for tumor therapy.

Supplemental Digital Content is available in the text., The efficacy of adoptive cellular immunotherapy against cancer cells is limited due to the presence of immunosuppressive cells within the solid tumor microenvironment. The upregulation of certain coinhibitory receptors may lead to exhaustion of the immune effector cells. T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an immune inhibitory receptor expressed by regulatory T cells and activated T cells and natural killer cells. The aim of this study was to determine the immunosuppressive effects of CD155/TIGIT signaling on CD8+ T cells of adoptive cellular immunotherapy in hepatocellular carcinoma (HCC). Our studies found that CD155 was overexpressed in HCC, and CD155hi HCC cells upregulated TIGIT on CD8+ T cells, which decreased the secretion of interferon-γ, tumor necrosis factor-α, and interleukin-17A and increased that of interleukin-10 from the effector cells. However, TIGIT blockade or CD155-knockdown reversed the inhibitory effect of HCC cells on CD8+ T-cell effector function. These results indicate that TIGIT can exert an immunosuppressive effect on CD8 T cells by modulating cytokine production through CD155, and is a promising target to optimize adoptive cellular immunotherapy against HCC.

Anti-thymocyte globulin (ATG) is a polyclonal antiserum introduced into clinical medicine more than 30 years ago. It induces a broad non-specific immunosuppression. In haematology, standard indications are severe aplastic anaemia and prophylaxis and treatment of graft-versus-host disease (GVHD) (after allogeneic transplantation). For aplastic anaemia, ATG from horses has been found to be superior to ATG from rabbits. In the situation of allogeneic transplantation, ATG lessens the risk of chronic GVHD but may not improve survival. There is current controversy regarding which patients benefit most from ATG and what the ideal dosage is. It is likely that in the coming years a more specific immunosuppressive will be developed that will minimize GVHD while maintaining the graft-versus-malignancy effect.

It has been demonstrated that mesenchymal stem cells (MSCs) have potent immunosuppressive capacities. But it is controversial whether differentiated mature stromal cells (SCs) share the immunosuppressive capacities. A previous study examined the ability of SCs from different human tissue sites to inhibit the proliferation of lymphocytes. The results are all positive but the mechanism isn't clear, and few mouse data have been published on this topic. Using an efficient mixed cell culture assay, our in vitro data show that the anti-proliferative ability of murine MSCs on lymphocytes is shared by mature murine SCs, i.e. chondrocytes and fibroblasts. Though conflicting results have been published, our results suggest that nitric oxide and IFN-γ are critical to the immunosuppressive effect. We also demonstrate that murine MSCs cultivated in chondrogenic differentiation medium still possess the anti-proliferative capacities on lymphocytes in vitro.

Stress has long been suspected to negatively influence cancer mortality, yet the molecular mechanisms responsible for this effect have only recently been identified. A new study identifies a stress-induced response in dendritic cells-the activation of the glucocorticoid-inducible transcriptional regulator TSC22D3-as a potent, immunosuppressive effect of stress on cancer.

Lupus nephritis (LN) is one of the most common and severe manifestations of systemic lupus erythematosus, leading to permanent renal damage and chronic kidney disease. Hydroxychloroquine (HCQ) serves a protective role against lupus-associated clinical manifestations and medical complications; however, it results in numerous adverse reactions, limiting its long-term use. The aim of the present study was to investigate the combined effect of HCQ and artemisinin (ART) on LN, and to elucidate the underlying mechanisms. An in vivo LN mouse model was prepared, and the animals were administered prednisone (PDS; serving as a positive control), high-dose HCQ (H-HCQ) or low-dose HCQ combined with ART (L-HCQ + ART) once daily for 8 weeks. The body weight, serum biochemical parameters, immune and inflammatory indicators, renal and spleen histological alterations, and mRNA expression levels of Kruppel-like factor 15 (KLF15) and nuclear factor-κB (NF-κB) were analyzed. It was observed that L-HCQ + ART and H-HCQ ameliorated the LN-induced body weight decrease, and significantly decreased the levels of anti-double stranded DNA, antinuclear antibodies, immunoglobulin G, interferon γ, tumor necrosis factor-α and transforming growth factor-β1, as well as improved the kidney and spleen pathology, when compared with the model group. In addition, L-HCQ + ART and H-HCQ treatments induced KLF15 upregulation and NF-κB downregulation. These results indicated that treatment with L-HCQ + ART exerted renoprotective effects by regulating the expression levels of cytokines, KLF15 and NF-κB. This combination treatment may have a similar immunosuppressive effect as PDS and H-HCQ, and may be a promising alternative for LN treatment.