Regulatory T cells (Tregs) are key mediators of immune suppression in cancer and are frequently elevated in hematologic malignancies, including acute and chronic leukemias, however, their role in modulating the leukemic cell phenotype and therapy response remains unclear. This study investigated whether natural Tregs (nTregs), in vitro-generated CD4+CD25+Foxp3+ Tregs (iTregs), and type 1 regulatory T (Tr1) cells directly modulate the phenotype, viability and drug response of the K562 chronic myeloid leukemia cell line in vitro. K562 cells were cultured either in direct co-culture with Treg subsets or in their culture supernatants, followed by flow cytometric assessment of stemness-associated and progression/drug-resistance-related markers. Anti-TGF-β1 or anti-IL-10 blocking antibodies were used to assess cytokine-dependent mechanisms. Functional effects were evaluated using an MTT-based assay under drug-free conditions or after treatment with daunorubicin or gemcitabine. Natural Tregs increased the proportion of CD34+, PDGFRβ+, ABCG2+ and VEGFR1⁺ K562 cells. Neutralization of TGF-β1 in the co-culture system partially attenuated the nTreg-associated upregulation of PDGFRβ and ABCG2. iTregs increased ABCG2 expression, which was also reduced upon TGF-β1 blockade. Tr1 cells increased the proportion of CD24⁺ cells, upregulated PDGFRβ and ABCG2, and increased K562 cell metabolic activity/viability under drug-free conditions. All Treg subsets attenuated daunorubicin cytotoxicity, whereas reduced sensitivity to gemcitabine was observed only in iTreg- and Tr1-containing cultures. These findings suggest that Treg cell subsets may directly promote stemness-associated and drug-tolerance-related features in K562 cells in vitro, supporting a tumor-promoting role within the leukemia microenvironment and warranting further validation in primary leukemia samples and in vivo models.

The active hormonal form of vitamin D, 1,25(OH)2D, regulates many components of the immune system and previous research shows that 1,25(OH)2D reduces the number and suppressive activity of MDSCs in tumors. This study aimed to evaluate the effects of calcitriol treatment on MDSCs in aged mice. We showed that aged BALB/c and CD1 mice exhibited increased levels of CD11b+Gr1+ cells in both the spleen and bone marrow compared to young mice. These cells displayed a less mature phenotype marked by reduced F4/80 expression and demonstrated robust T cell suppressive activity, as evidenced by their ability to inhibit the production of IFNγ and TNFα. Treatment of aged mice with calcitriol, administered twice weekly at a dose equivalent to 1 µg/kg for 4 weeks, significantly increased the population of CD11b+Gr1+ cells in the spleen, but not in the bone marrow of the animals, and promoted their differentiation into a more mature phenotype characterized by elevated F4/80 expression. In addition, calcitriol-treated aged mice exhibited significantly improved T cell responses, as indicated by increased IFNγ production upon specific antigen stimulation compared to the control group of mice. In vitro, calcitriol treatment of bone marrow-derived MDSCs similarly enhanced F4/80 expression without altering other markers such as CD11b, CD11c, or MHCII, and led to reduced expression of reactive oxygen species by these cells. Our study highlights the consistency of MDSC expansion across inbred and outbred mouse strains and supports the immunomodulatory role of calcitriol in promoting MDSC maturation and alleviating immune suppression in aging.

Inflammation is a self-defense mechanism that controls the homeostasis of an organism, and its alteration by persistent noxious stimuli could lead to an imbalance in the regulation of inflammatory responses mediated by innate and adaptive immunity. During chronic inflammation, sustained exposure of myeloid cells to the various inflammatory signals derived from inflamed tissue could lead to the generation of myeloid cells with an immunosuppressive state, called myeloid-derived suppressor cells (MDSCs), which can exert protective or deleterious functions depending on the nature of signals and the specific inflammatory conditions created by different pathophysiological contexts. Initially identified in various tumor models and cancer patient samples, these cells have long been recognized as negative regulators of anti-tumor immunity. Consequently, researchers have focused on elucidating the molecular mechanisms underlying their potent immunosuppressive activity. As a key component of the signal transducing processes, protein kinases play a central role in regulating the signal transduction mechanisms of many cellular activities, including differentiation and immunosuppression. Over the past decade, at least a dozen kinases, including mechanistic target of rapamycin (mTOR), phosphoinositide 3-kinases (PI3Ks), TAM (Tyro3, Axl, Mer) family of receptor tyrosine kinases (TAM RTKs), mitogen-activated protein kinases (MAPKs), and others, have emerged as key contributors to the generation and differentiation of MDSCs. Here, we discuss the recent findings on these kinases that directly contribute to the immunosuppressive functions of MDSCs.

Monocytes play a crucial role in the immune response against pathogens. Here, we sought to determine COVID-19 and the vaccine Gam-COVID-Vac induce long-term changes in the phenotype and cytokine production of circulating monocytes. Monocytes were purified from peripheral blood mononuclear cells of healthy donors who had not had COVID-19 or vaccination, who had received two doses of Gam-COVID-Vac, and who had mild/moderate COVID-19 in the last 6 months and evaluated by flow cytometry. To investigate the effect of SARS-CoV-2 proteins, monocytes were cultured for 2 days with or without stimulation with recombinant SARS-CoV-2 S1 and N peptides. Monocytes obtained from vaccinated and recovered individuals showed increased basal expression of HLA-DR, CD63, CXCR2, and TLR7. We also observed an increased frequency of CD63 + classical monocytes in both groups, as well as an increased frequency of HLA-DR + non-classical monocytes in the COVID-19-recovered group compared to the control group. Monocytes from vaccinated and recovered donors produced higher basal levels of IL-6, IL-1β, and TNF-α cytokines. Ex vivo stimulation with SARS-CoV-2 antigens induced increased expression of HLA-DR and TLR7 on monocytes obtained from the control group. The challenge with SARS-CoV-2 antigens had no effect on the production of IL-6, IL-1β, and TNF-α cytokines by monocytes. The acquired data offer compelling evidence of enduring alterations in both the phenotype and functional status of circulating monocytes subsequent to vaccination with Gam-COVID-Vac and mild/moderate COVID-19 infection. At least some of these changes appear to be a consequence of exposure to SARS-CoV-2 S1 and N antigens.

Myeloid-derived suppressor cells (MDSCs) are an immunosuppressive population involved in pathological processes associated with chronic inflammation. In recent years, the role of these cells in the regulation of a number of non-pathological processes, in particular, in the development of vaccine-induced immune response, has been actively discussed. This work was aimed at investigating the role of MDSC in the development of an immune response in old mice immunized with an inactivated whole virion SARS-CoV-2. Immunization of old animals induced an increase in the relative content of B cells and the production of specific antibodies to S1 and N proteins of SARS-CoV-2 in titers comparable to those of young animals. At the same time, elevated MDSC levels in aged animals negatively correlated with the level of CD8+ T cells. Splenic MDSCs in old animals were characterized by increased production of reactive oxygen species compared to young animals. In vitro experiments showed that MDSC depletion increased antigen-specific production of IFNγ by CD4+ T cells. The data obtained suggest a negative role for MDSC in regulating the T-cell vaccine-induced response to inactivated SARS-CoV-2 and encourage further studies in this direction, which may be a key to developing approaches to increase the efficacy of vaccines against SARS-CoV-2 in at-risk groups.

Regulatory T cells (Treg cells) play a crucial role in regulation of immune response. It is believed that excessive activity of Treg cells in the early stages of infectious diseases reduces the pro-inflammatory activity of cells in the innate and adaptive immune response, thereby contributing to the development of chronic inflammation or excessive inflammation. Additionally, it is known that aging leads to changes in the quantity of Treg cells and disrupts their activity. It is established that infection with the SARS-CoV-2 virus leads to fatal and severe cases of the disease, primarily among the elderly population. However, the underlying cause of the development of severe forms in elderly individuals remains incompletely understood. Thus, we hypothesized that the dysregulation of the Treg cell activity in elderly individuals may contribute to the development of severe forms and lethality from SARS-CoV-2, leading to the emergence of hyper inflammation in this population. To investigate the impact of SARS-CoV-2 on the immunosuppressive properties of Treg cells, venous blood samples were obtained from young healthy volunteers and elderly individuals. Dendritic cells were obtained by PBMC adhesion on plastic. Adherent monocytes were cultured in cytokine medium with interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-SCF), with addition of lipopolysaccharide (LPS) after 48 hours and incubated for an additional 24 hours with S1 or N antigens of SARS-CoV-2 virus. The obtained dendritic cells presenting SARS-CoV-2 antigens were then co-cultured with autologous CD4+-T lymphocytes ex vivo. The expression level of immunosuppressive membrane-associated and soluble molecules expressed by Treg cells was assessed using flow cytometry. Our results indicate that the immunosuppressive activity of Treg cells exhibits contrasting patterns in the two donor groups studied in response to the presentation of SARS-CoV-2 antigens. The proportion of Treg cells, as well as the expression levels of the immunosuppressive molecules, including tumor growth factor beta (TGF-b), CD39, glucocorticoid-induced tumor necrosis factor receptor-related (GITR) protein, and the levels of the intracellular immunosuppressive cytokines, including IL-10 and IL-35, in Treg cells obtained from peripheral blood of elderly donors, significantly increased in response to the presentation of SARS-CoV-2 antigens ex vivo, when compared to the group of young donors. Conversely, in the group of young donors were observed a decrease in the expression of these markers and an increase in the concentration of extracellular pro-inflammatory cytokines IL-2 and IFN-γ ex vivo, which activate the effector immune cells and contribute to virus elimination. In summary, the presented results suggest that Treg cells derived from elderly individuals exhibit elevated immunosuppressive activity in response to SARS-CoV-2 antigens ex vivo. Obtained results may indicate that in elderly individuals on the early stages of SARS-CoV-2 infection Treg cells may also possess enhanced immunosuppressive activity, which may contribute to the overall suppression of anti-viral immune responses, thereby potentially leading to the delayed SARS-CoV-2 virus clearance and development of severe forms of the disease.

Preventive vaccination is a crucial strategy for controlling and preventing infectious diseases, offering both effectiveness and cost-efficiency. However, despite the widespread success of vaccination programs, there are still certain population groups who struggle to mount adequate responses to immunization. These at-risk groups include but are not restricted to the elderly, overweight individuals, individuals with chronic infections and cancer patients. All of these groups are characterized by persistent chronic inflammation. Recent studies have demonstrated that one of the key players in immune regulation and the promotion of chronic inflammation are myeloid-derived suppressor cells (MDSCs). These cells possess a wide range of immunosuppressive mechanisms and are able to dampen immune responses in both antigen-specific and antigen-nonspecific manner, thus contributing to the establishment and maintenance of an inflammatory environment. Given their pivotal role in immune modulation, there is growing interest in understanding how MDSCs may influence the efficacy of vaccines, particularly in vulnerable populations. In this narrative review, we discuss whether MDSCs are able to regulate vaccine-induced immunity and whether their suppression can potentially enhance vaccine efficacy in vulnerable populations.

В декабре 2019 года впервые был зафиксирован вирус SARS-CoV-2, положивший начало пандемии COVID-19. Это инфекционное заболевание поражает дыхательную систему человека, вызывая различные осложнения со стороны жизненно важных органов человека. За пару лет коронавирусная инфекция привела к многочисленным смертям, нанося огромный вред иммунной системе людей. В частности, вирус наиболее опасен для пожилых людей, которые составляют группу риска заражения инфекцией. В последние годы наблюдается увеличение доли людей пожилого возраста практически во всех странах. Наиболее эффективным способом борьбы с COVID-19 является вакцинация. Возрастной фактор и сопутствующие болезни пациентов могут играть значительную роль в эффективности вакцинации от COVID-19. Поэтому важно изучить влияние вакцин на иммунный ответ у пожилых людей при хронических воспалительных заболеваниях. В данном обзоре предоставляется обобщение имеющейся информации об эффективности вакцинации у пожилых людей с наиболее часто встречающимися хроническими воспалительными заболеваниями: сахарным диабетом, ожирением, остеопорозом и атеросклерозом. In December 2019, the SARS-CoV-2 virus was first detected, which marked the beginning of the COVID-19 pandemic. This infectious disease affects the human respiratory system, causing various complications from the vital organs of a person. In a couple of years, coronavirus infection has led to numerous deaths, causing huge damage to the immune system of people. In particular, the virus is most dangerous for the elderly, who are at risk of infection. In recent years, there has been an increase in the proportion of elderly people in almost all countries. The most effective way to combat COVID-19 is vaccination. The age factor and concomitant diseases of patients can play a significant role in the effectiveness of vaccination against COVID-19. Therefore, it is important to study the effect of vaccines on the immune response in elderly people with chronic inflammatory diseases. This review summarizes the available information on the effectiveness of vaccination in elderly people with the most common chronic inflammatory diseases: diabetes mellitus, obesity, osteoporosis and atherosclerosis. 2019 жылдың желтоқсанында SARS-CoV-2 вирусы алғаш рет тіркеліп, COVID-19 пандемиясын бастады. Бұл жұқпалы ауру адамның тыныс алу жүйесіне әсер етеді, адамның өмірлік маңызды мүшелерінің әртүрлі асқынуларын тудырады. Бірнеше жыл ішінде коронавирустық инфекция адамдардың иммундық жүйесіне үлкен зиян келтіріп, өлім-жетім санының жоғарлауына әкелді. Атап айтқанда, вирус инфекцияны жұқтыру қаупі бар егде жастағы адамдар үшін ең қауіпті. Соңғы жылдары барлық елдерде егде жастағы адамдардың үлесінің артуы байқалды. COVID-19-бен күресудің ең тиімді әдісі-вакцинация. Жас факторы және пациенттердің ілеспе аурулары COVID-19 вакцинациясының тиімділігінде маңызды рөл атқаруы мүмкін. Сондықтан созылмалы қабыну аурулары кезінде егде жастағы адамдарда вакциналардың иммундық реакцияға әсерін зерттеу маңызды. Бұл шолуда созылмалы қабыну аурулары: қант диабеті, семіздік, остеопороз және атеросклероз бар егде жастағы адамдарда вакцинацияның тиімділігі туралы қолда бар ақпаратты жинақтау ұсынылады. Түйінді сөздер: COVID-19, вакцинация, егде жас, қант диабеті, семіздік, остеопороз, атеросклероз.

Abstract According to WHO, the acquired secondary form of hematopoietic-depressive states increases the risk of death in people with cancer, infectious, and hormonal diseases. The choice of drugs that stimulate the proliferative activity of bone marrow cells is limited. The stimulus to the search for hematopoietic-stimulating compounds among pyridine derivatives was the manifestation of the activity of the cerebroprotective drug Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) to restore the granulocytes and B-lymphocytes homeostasis in clinical practice. The hematopoietic-stimulating activity of the newly synthesized compound Complex of 5-benzyl-7-(o-fluorobenzylidene)-2,3-bis(o-fluorophenyl)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo [4,3-c]pyridine complex with β-cyclodextrin (BIV) was studied on a model of cyclophosphamide-induced myelodepression in C57BL6/J mouse line. The BIV compound demonstrated a stimulating effect on the process of restoring the level of Ly-6G+ Ly-6C+ granulocytes, monocytes/macrophages, CD19+ B-lymphocytes in the bone marrow, exceeding the activity of the reference drug Methyluracil. The BIV compound did not affect on the proliferative activity of c-kit (CD117+)-expressing cells, CD3e+ pre-T-lymphocytic cells and Ter-119+ erythroid cells in the bone marrow. The total number of bone marrow myelokaryocytes in the experimental groups was significantly higher than in the intact group. The pronounced hematopoietic-stimulating effect of the BIV compound gives in the future the prospect of development as a drug used for the treatment of B-lymphocytic and granulocytic-macrophage hematopoietic-depressive states.

Увеличение доли пожилых людей в общей численности населения отмечается практически во всем мире. С возрастом увеличивается частота инфекционных и онкологических заболеваний, а также снижается эффективность вакцинации. Считается, что это вызвано нарушениями в работе иммунной системы, называемых иммуностарением, и связано со снижением активности адаптивного иммунного ответа и развитием системного хронического воспаления как инфекционной, так и неинфекционной природы, возрастным воспалением, которое прежде всего связывают с нарушением механизмов клеточного клиренса необходимых для разрешения воспаления после инфильтрации патогена или повреждения ткани, и, как следствие, хронической активации врожденного иммунного ответа. При этом, именно возрастные дисфункции моноцитов и нейтрофилов, которые выражаются в повышении уровня противоспалительных медиаторов и нарушении фагоцитоза, играют одну из основных ролей в возрастном воспалении – инфламэйджинге (inflammaging).Целью данного обзора является обобщение имеющихся данных об изменениях фенотипа и функциональной активности моноцитов и нейтрофилов при старении и обсуждение их роли в развитии инфекционных заболеваний у пожилых людей. The elderly increasing proportion in the general population is observed in almost all over the world. Aging is associated with an increased incidence of infectious diseases and cancers, as well as a decreased effectiveness of vaccinations. It is considered that increased morbidity observed with age is caused by immune system disfunction, called immunosenescence, and is associated with a decreased activity of adaptive immune response. However, not all aspects of immunity decline with age; aging is also associated with systemic chronic inflammation of both infectious and non-infectious nature, called "inflammaging," which is primarily associated with impaired cellular clearance mechanisms, which are necessary to resolve inflammation after pathogen infiltration or tissue damage, and, consequently, with chronic activation of the innate immune response. At the same time age-related dysfunction of monocytes and neutrophils manifested by increased levels of proinflammatory mediators and impaired phagocytosis plays one of the major role in the inflammatory response.The purpose of this review is to summarize available data of phenotype and functional activity of monocytes and neutrophils changes during aging and discuss their role in the development of infectious diseases in elderly people.

Coronavirus disease 2019 (COVID-19) is a potentially life-threatening infection characterized by excessive inflammation, coagulation disorders and organ damage. A dysregulated myeloid cell compartment is one of the most striking immunopathologic signatures of this newly emerged infection. A growing number of studies are reporting on the expansion of myeloid cells with immunoregulatory activities in the periphery and airways of COVID-19 patients. These cells share phenotypic and functional similarities with myeloid-derived suppressor cells (MDSCs), which were first described in cancer patients. MDSCs are a heterogeneous population of pathologically activated myeloid cells that exert immunosuppressive activities against mainly effector T cells. The increased frequency of these cells in COVID-19 patients suggests that they are involved in immune regulation during this infection. In this article, we review the current findings on MDSCs in COVID-19 and discuss the complex role of these cells in the immunopathology of COVID-19.

Impaired NK cytotoxicity has been linked to poor cancer prognosis, but its mechanisms are not clearly established. Increasing data demonstrate that NK cells lose cytotoxicity after interaction with NK cell-sensitive tumor cells. In this paper, we provide evidence that the human adenocarcinoma cell line MiaPaCa2 and TNFα and TGFβ-treated MiaPaCa2 cultures (MiaPaCa2-TT) induced functional anergy of NK cells via FGL2 protein. MiaPaCa2-TT cultures decreased expression of IFNγ, CD107a, DNAM-1, and stimulated expression of PD1 by NK cells, as well as inhibited their cytotoxic activity in a greater manner compared to the parental culture. More importantly, we found that co-cultivation with anergized NK cells decreased expression of IFNγ and CD107a by naïve NK cells, which supports the hypothesis of NK cell functional anergy transmission. The obtained results suggest a mechanism by which tumor cells may inhibit cytotoxic functions of tumor-infiltrating and circulating NK cells in cancer.Abbreviations: CFSE: Carboxyfluorescein diacetate succinimidyl ester; CSCs: Cancer stem cells; FGL2: Fibrinogen-like protein 2; mAbs: Monoclonal antibodies; MiaPaCa2: Human adenocarcinoma cell line; MiaPaCa2-ТТ: Adenocarcinoma cell line MiaPaCa2 cells stimulated with TNFα and TGFβ-1; PI: Propidium iodide; TGFβ: Transforming growth factor beta; TME: Tumor microenvironment; TNFα: Tumor necrosis factor alfa.

Инфекционные заболевания у пожилых людей значительно более часты и смертность от них выше, чем у молодых людей. Вакцинация является наиболее эффективной и наименее затратной профилактической мерой при ряде инфекционных заболеваний. Однако вакцины, которые эффективны у молодых людей, часто неэффективны у пожилых людей старше 65 лет, причиной чего является постепенное снижение функциональных возможностей иммунной системы, происходящее с возрастом и называемое иммуностарением. Связанные с возрастом изменения в клеточном и гуморальном иммунитете ухудшают первичный ответ на вакцины и ослабляют развитие долговременной иммунной памяти. Исследования последних лет дают основание предполагать, что одной из возможных причин возникновения и поддержания иммуностарения в организме могут быть миелоидные супрессорные клетки ( Myeloid-Derived Suppressor Cells, MDSC ). Многочисленными исследованиями установлено, что MDSC способны ингибировать функции клеток врожденного и адаптивного иммунитета посредством ряда механизмов. В настоящем обзоре приводятся сведения, подчеркивающие роль MDSC в ингибировании иммунного ответа на вакцины при старении, а также обосновываются возможные пути преодоления данного иммунного препятствия. Infectious diseases in older people are much more frequent, and mortality from them is higher than in young people. Vaccination is the most effective and least expensive preventative measure for a number of infectious diseases. However, vaccines that are effective in young people are often ineffective in older people over 65, which is a result of a gradual decrease in the functional capacity of the immune systems, which occurs with age, and is called «immunosenescence». Age-related changes in the cellular and humoral immunity worsen the primary response to vaccines and weaken the development of long-term immunological memory. Recent studies suggest that one of the possible causes of the occurrence and maintenance of «immunosenescence» may be myeloid-derived suppressor cells ( MDSCs ). These cells have been shown to inhibit the functions of innate and adaptive immunity cells through a number of mechanisms. In this review, we provide information that emphasizes the role of MDSCs in inhibiting the immune response to vaccines during aging, and also substantiates possible ways to overcome this immunological obstacle.

It is well documented that age-related impaired functioning of immunocompetent cells is associated with an increase in the rates of chronic inflammatory diseases. Recently, an ability of melatonin to modulate inflammatory processes by regulating leucocyte recruitment has been demonstrated. However, to date, no studies have attempted to determine the impact of melatonin on the expression of CD62L by lymphocytes. CD62L, also known as L-selectin, is required for the entry of lymphocytes into secondary lymphoid organs, sites of tumor growth and chronic inflammation through high endothelial venules. Here, we investigated the effect of melatonin at physiological concentrations on the expression of CD62L by T and NK cells in vivo and in vitro. We demonstrated that NK and CD3(+) T cells obtained from the spleen of aged mice were characterized by decreased expression of CD62L compared to young mice. Melatonin administration up-regulated the levels of surface CD62L on NK and T cell populations in aged mice under non-inflammatory conditions and on CD8(+) T cells in aged mice with chronic inflammation. Pre-incubation with melatonin prevented the reduction in CD62L expression by CD8(+) T cells induced by the co-cultivation of peripheral blood mononuclear cells with human pancreatic adenocarcinoma cell line (MiaPaCa-2). The obtained results suggest that melatonin can modulate lymphocyte homing into lymph nodes and sites of chronic inflammation and, therefore, can stimulate immune responses in chronic inflammatory conditions associated with aging.

EXPANSION OF CD62L-EXPRESSING MYELOID-DERIVED SUPPRESSOR CELLS IN INFLAMMATION- RELATED TUMOR PROGRESSION

Recent data have demonstrated that chronic inflammation is a crucial component of tumor initiation and progression. We previously reported that immature myeloid-derived suppressor cells (MDSCs) with immunosuppressive activity toward effector T cells were expanded in experimental chronic inflammation. We hypothesized that elevated levels of MDSCs, induced by chronic inflammation, may contribute to the progression of tumor growth. Using the Ehrlich carcinoma animal model, we found increased tumor growth in mice with chronic adjuvant arthritis, which was accompanied by a persistent increase in the proportion of splenic monocytic and granulocytic MDSCs expressing CD62L (L-selectin), when compared to tumor mice without adjuvant arthritis. Depletion of inflammation-induced MDSCs resulted in decreased tumor growth. In vitro studies demonstrated that increased expression of CD62L by MDSCs was mediated by TNFα, elevated concentrations of which were found in tumor mice subjected to chronic inflammation. Moreover, the addition of exogenous TNFα markedly enhanced the suppressive activity of bone marrow-derived MDSCs, as revealed by the ability to impair the proliferation of CD8+ T cells in vitro. This study provides evidence that chronic inflammation may promote tumor growth via induction of CD62L expression by MDSCs that can facilitate their migration to tumor and lymph nodes and modulation of their suppressor activity.

Myeloid-derived suppressor cells (MDSCs) are important negative regulators of immune processes in cancer and other pathological conditions. We suggested that MDSCs play a key role in pathogenesis of chronic inflammation, which precedes and, to a certain extent, induces carcinogenesis. The present study aimed at investigation of MDSCs arising during chronic inflammation and light-at-night (LN)-induced stress, which is shown to accelerate chronic diseases.