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Nutrition may affect animal health due to the strong link between them. Also, diets improve the healing process in various disease states. Cancer is a disease, where the harmful consequences of tumors severely impair the body. The information regarding the evolution of this disease is extrapolated from human to animal because there are few specific studies regarding nutritional needs in animals with cancer. Thus, this paper aims to review the literature regarding the immunomodulatory effects of vitamins in mammal cancer. An adequate understanding of the metabolism and requirements of nutrients for mammals is essential to ensuring their optimal growth, development, and health, regardless of their food sources. According to these: 1) Some species are highly dependent on vitamin D from food, so special attention must be paid to this aspect. Calcitriol/VDR signaling can activate pro-apoptotic proteins and suppress antiapoptotic ones. 2) Nitric oxide (NO) production is modulated by vitamin E through inhibiting transcription nuclear factor kappa B (NF-kB) activation. 3) Thiamine supplementation could be responsible for the stimulation of tumor cell proliferation, survival, and resistance to chemotherapy. 4) Also, it was found that the treatment with NO-Cbl in dogs is a viable anti-cancer therapy that capitalizes on the tumor-specific properties of the vitamin B12 receptor. Therefore, diets should contain the appropriate class of compounds in adequate proportions. Also, the limitations of this paper are that some vitamins are intensively studied and at the same time regarding others, there is a lack of information, especially in animals. Therefore, some subsections are longer and more heavily debated than others. [ABSTRACT FROM AUTHOR]

This document is an editorial from the journal Frontiers in Immunology that focuses on the contributions of women in the field of cytokines and soluble factors in immunity. It features over 60 research papers written by female scientists from around the world, covering a range of topics including invertebrate and mammalian immunity, the role of cytokines in diseases, and the use of soluble factors as diagnostic and prognostic markers. The editorial emphasizes the dedication and collaboration of female scientists in scientific research. It also highlights successful women in the field, such as economist Claudia Goldin and biochemist Katalin Karicó, and discusses the challenges faced by women in science. The document underscores the importance of promoting women's participation in science and addressing gender disparities. [Extracted from the article]

Papillary thyroid cancer (PTC) is the most common type of primary thyroid cancer. Despite the low malignancy and relatively good prognosis, some PTC cases are highly aggressive and even develop refractory cancer in the thyroid. Growing evidence suggested that microenvironment in tumor affected PTC biological behavior due to different immune states. Different interconnected components in the immune system influence and participate in tumor invasion, and are closely related to PTC metastasis. Immune cells and molecules are widely distributed in PTC tissues. Their quantity and proportion vary with the host's immune status, which suggests that immunotherapy may be a very promising therapeutic modality for PTC. In this paper, we review the role of immune cells and immune checkpoints in PTC immune microenvironment based on the characteristics of the PTC tumor microenvironment. [ABSTRACT FROM AUTHOR]

While the general population regained a certain level of normalcy with the end of the global health emergency, the risk of contracting COVID-19 with a severe outcome is still a major concern for people with compromised immunity. This paper reviews the impact of COVID-19 on people with immunocompromised status, identifies the gaps in the current management landscape, and proposes actions to address this unmet need. Observational studies have demonstrated that people with immune dysfunction have a higher risk of COVID-19-related hospitalization and death, despite vaccination, than the general population. More research is needed to define the optimal prevention and treatment strategies that are specific to people with immunocompromised status, including novel vaccination strategies, monoclonal antibodies that provide passive immunity and complement suboptimal vaccination responses, and improved and safer antiviral treatment for COVID-19. Preventive measures beyond vaccination alone are urgently needed to protect this vulnerable population. [ABSTRACT FROM AUTHOR]

This document is an editorial published in Frontiers in Immunology titled "Interdependencies and interfaces in bone regeneration - the immune status at its core." The editorial discusses the importance of understanding the immune reaction in bone healing and regeneration. It highlights the interdependencies and interfaces between the immune system and other factors such as mechanics, metabolism, revascularization, and aging. The editorial also mentions that this Research Topic includes nine papers from authors around the world, covering various aspects of bone regeneration. [Extracted from the article]

This document is an editorial published in the journal Frontiers in Immunology. It discusses the role of adaptive immunity in atherosclerosis, a condition that contributes to acute cardiovascular events. The editorial highlights the importance of chronic inflammation in atherosclerosis and the potential for new intervention strategies. It also explores the use of new immunological techniques to study the role of the adaptive immune system in the development, progression, and regression of atherosclerosis. The document includes summaries of several research papers that investigate different aspects of adaptive immunity in atherosclerosis, including T cell and B cell responses. Overall, the editorial provides an overview of the latest findings in this field and serves as a valuable resource for researchers interested in studying adaptive immunity in atherosclerosis. [Extracted from the article]

The tumor microenvironment, particularly the immune microenvironment, plays an indispensable role in the malignant progression and metastasis of gastric cancer (GC). As our understanding of the GC microenvironment continues to evolve, we are gaining deeper insights into the biological mechanisms at the single-cell level. This, in turn, has offered fresh perspectives on GC therapy. Encouragingly, there are various monotherapy and combination therapies in use, such as immune checkpoint inhibitors, adoptive cell transfer therapy, chimeric antigen receptor T cell therapy, antibody-drug conjugates, and cancer vaccines. In this paper, we review the current research progress regarding the GC microenvironment and summarize promising immunotherapy research and targeted therapies. [ABSTRACT FROM AUTHOR]

Ovarian cancer remains a challenging disease with limited treatment options and poor prognosis. The tumor microenvironment (TME) plays a crucial role in tumor growth, progression, and therapy response. One characteristic feature of the TME is the abnormal tumor vasculature, which is associated with inadequate blood perfusion, hypoxia, and immune evasion. Vascular normalization, a therapeutic strategy aiming to rectify the abnormal tumor vasculature, has emerged as a promising approach to reshape the TME, enhance antitumor immunity, and synergize with immunotherapy in ovarian cancer. This review paper provides a comprehensive overview of vascular normalization and its potential implications in ovarian cancer. In this review, we summarize the intricate interplay between anti-angiogenesis and immune modulation, as well as ICI combined with anti-angiogenesis therapy in ovarian cancer. The compelling evidence discussed in this review contributes to the growing body of knowledge supporting the utilization of combination therapy as a promising treatment paradigm for ovarian cancer, paving the way for further clinical development and optimization of this therapeutic approach. [ABSTRACT FROM AUTHOR]

Besides dividing the organism's immune system into adaptive and innate immunity, it has long been thought that only adaptive immunity can establish immune memory. However, many studies have shown that innate immunity can also build immunological memory through epigenetic reprogramming and modifications to resist pathogens' reinfection, known as trained immunity. This paper reviews the role of mitochondrial metabolism and epigenetic modifications and describes the molecular foundation in the trained immunity of arthropods and mollusks. Mitochondrial metabolism and epigenetic modifications complement each other and play a key role in trained immunity. [ABSTRACT FROM AUTHOR]

The immune system plays a complex role in tumor formation and development. On the one hand, immune surveillance can inhibit the growth of tumors; on the other hand, immune evasion of tumors can create conditions conducive for tumor development and growth. CircRNAs are endogenous non-coding RNAs with a covalently closed loop structure that are abundantly expressed in eukaryotic organisms. They are characterized by stable structure, rich diversity, and high evolutionary conservation. In particular, circRNAs play a vital role in the occurrence, development, and treatment of tumors through their unique functions. Recently, the incidence and mortality of digestive cancers, especially those of gastric cancer, colorectal cancer, and liver cancer, have remained high. However, the functions of circRNAs in digestive cancers immunity are less known. The relationship between circRNAs and digestive tumor immunity is systematically discussed in our paper for the first time. CircRNA can influence the immune microenvironment of gastrointestinal tumors to promote their occurrence and development by acting as a miRNA molecular sponge, interacting with proteins, and regulating selective splicing. The circRNA vaccine even provides a new idea for tumor immunotherapy. Future studies should be focused on the location, transportation, and degradation mechanisms of circRNA in living cells and the relationship between circRNA and tumor immunity. This paper provides a new idea for the diagnosis and treatment of gastrointestinal tumors. [ABSTRACT FROM AUTHOR]

Introduction: Ageing research is establishing macrophages as key immune system regulators that undergo functional decline. Due to heterogeneity between species and tissue populations, a plethora of data exist and the power of scientific conclusions can vary substantially. This meta-analysis by information content (MAIC) and systematic literature review (SLR) aims to determine overall changes in macrophage gene and protein expression, as well as function, with age. Methods: PubMed was utilized to collate peer-reviewed literature relating to macrophage ageing. Primary studies comparing macrophages in at least two age groups were included. Data pertaining to gene or protein expression alongside method used were extracted for MAIC analysis. For SLR analysis, data included all macrophage-specific changes with age, as well as species, ontogeny and age of groups assessed. Results: A total of 240 studies were included; 122 of which qualified for MAIC. The majority of papers focussed on changes in macrophage count/infiltration as a function of age, followed by gene and protein expression. The MAIC found iNOS and TNF to be the most commonly investigated entities, with 328 genes and 175 proteins showing consistent dysregulation with age across the literature. Overall findings indicate that cytokine secretion and phagocytosis are reduced and reactive oxygen species production is increased in the ageing macrophage. Discussion: Collectively, our analysis identifies critical regulators in macrophage ageing that are consistently dysregulated, highlighting a plethora of targets for further investigation. Consistent functional changes with age found here can be used to confirm an ageing macrophage phenotype in specific studies and experimental models. [ABSTRACT FROM AUTHOR]

Nutrition may affect animal health due to the strong link between them. Also, diets improve the healing process in various disease states. Cancer is a disease, where the harmful consequences of tumors severely impair the body. The information regarding the evolution of this disease is extrapolated from human to animal because there are few specific studies regarding nutritional needs in animals with cancer. Thus, this paper aims to review the literature regarding the immunomodulatory effects of vitamins in mammal cancer. An adequate understanding of the metabolism and requirements of nutrients for mammals is essential to ensuring their optimal growth, development, and health, regardless of their food sources. According to these: 1) Some species are highly dependent on vitamin D from food, so special attention must be paid to this aspect. Calcitriol/VDR signaling can activate pro-apoptotic proteins and suppress anti-apoptotic ones. 2) Nitric oxide (NO) production is modulated by vitamin E through inhibiting transcription nuclear factor kappa B (NF-κB) activation. 3) Thiamine supplementation could be responsible for the stimulation of tumor cell proliferation, survival, and resistance to chemotherapy. 4) Also, it was found that the treatment with NO-Cbl in dogs is a viable anti-cancer therapy that capitalizes on the tumor-specific properties of the vitamin B12 receptor. Therefore, diets should contain the appropriate class of compounds in adequate proportions. Also, the limitations of this paper are that some vitamins are intensively studied and at the same time regarding others, there is a lack of information, especially in animals. Therefore, some subsections are longer and more heavily debated than others.

Food allergy is a serious public health problem because of its high incidence and risk. Probiotics can induce immune regulation in patients with allergic diseases, but its mechanism is not fully clear. In this paper, b-lactoglobulin (bLG)-sensitized mice were used as models to explore the mechanism of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) on reducing allergic reactions and regulating immune cell function. The results showed that oral administration of KV9 and FN3 significantly reduced the scores of allergic symptoms, hypothermia symptoms, and serum levels of bLG-specific immunoglobulins E (b-LG-sIgE), histamine, and mast cell protease in allergic mice. Flow cytometry analysis of intestinal dendritic cells (DCs) showed that the proportion of CD11c+major histocompatibility complex (MHC)-II+DCs, CD11c+CD80+DCs, and CD11c+ CD86+DCs increased after KV9 and FN3 intervention, indicating that the strains induced immature DCs and decreased the antigen-presenting capacity of DCs. Meanwhile, the toll-like receptor 4 (TLR4)-NF-kB signaling pathway was activated in DCs. The secretion of interleukin-12 (IL-12) was significantly increased, while interleukin-4 (IL-4) was decreased by DCs after KV9 and FN3 intervention, indicating that DCs have the potential to promote T-cell differentiation into T helper type 1 (Th1) cells. Furthermore, the proportion of CD3+CD8−IFN-g+ T cells in the spleen increased, while CD3+CD8−IL-4+T cells decreased after oral administration of KV9 and FN3, correcting the T helper type 2 (Th2)-skewed immune responses. These results indicate that KV9 and FN3 reduce b-LGinduced allergic symptoms in mice, and suggest that the two potential probiotics might be used as an alternative therapeutic agent for mitigating food allergy. [ABSTRACT FROM AUTHOR]

The adaptive immune response induced by SARS-CoV-2 plays a key role in the antiviral process and can protect the body from the threat of infection for a certain period of time. However, owing to the limitations of clinical studies, the antiviral mechanisms, protective thresholds, and persistence of the immune memory of adaptive immune responses remain unclear. This review summarizes existing research models for SARS-CoV-2 and elaborates on the advantages of animal models in simulating the clinical symptoms of COVID-19 in humans. In addition, we systematically summarize the research progress on the SARS-CoV-2 adaptive immune response and the remaining key issues, as well as the application and prospects of animal models in this field. This paper provides direction for in-depth analysis of the anti-SARS-CoV-2 mechanism of the adaptive immune response and lays the foundation for the development and application of vaccines and drugs. [ABSTRACT FROM AUTHOR]

Keywords: parasite; helminth; protozoa; Apicomplexa; flagellate; co-infection; immunity; vaccines EN parasite helminth protozoa Apicomplexa flagellate co-infection immunity vaccines 1 4 4 05/11/20 20200507 NES 200507 This Research Topic, "Immunoparasitology: A unique interplay between host and pathogen", was intended to emphasize broadly the latest advances in immunoparasitology and has been concluded with more than 30 high quality papers encompassing aspects of parasite biology, host-parasite responses and interactions, and up-to-date control measures. The author emphasizes the fact that co-infection is a common occurrence in the field, where malarial parasites, soil-transmitted helminths, bacteria and viruses, are the causes for chronic infections in a large proportion of the population. The study by Rajamanickam et al. illustrates that I Strongyloides stercoralis i infection promotes the level of eosinophil, neutrophil, and mast cell granule proteins present in peripheral blood, while anthelmintic drug treatment suppresses them, indicating a direct involvement of activated granulocytes during helminth infection. Parasite, helminth, protozoa, Apicomplexa, flagellate, co-infection, immunity, vaccines. [Extracted from the article]

Multiple myeloma (MM) is the third most common malignant neoplasm of the hematological system. It often develops from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) precursor states. In this process, the immune microenvironment interacts with the MM cells to exert yin and yang effects, promoting tumor progression on the one hand and inhibiting it on the other. Despite significant therapeutic advances, MM remains incurable, and the main reason for this may be related to the complex and variable immune microenvironment. Therefore, it is crucial to investigate the dynamic relationship between the immune microenvironment and tumors, to elucidate the molecular mechanisms of different factors in the microenvironment, and to develop novel therapeutic agents targeting the immune microenvironment of MM. In this paper, we review the latest research progress and describe the dual influences of the immune microenvironment on the development and progression of MM from the perspective of immune cells and molecules. [ABSTRACT FROM AUTHOR]

Background: IL-37 is a recently identified cytokine with potent immunosuppressive functions. The research fronts of IL-37 are worth investigating, and there is no bibliometric analysis in this field. The purpose of this study is to construct the intellectual base and predict research hotspots of IL-37 research both quantitatively and qualitatively according to bibliometric analysis. Methods: The articles were downloaded from the Web of Science Core Collection (WoSCC) database from the inception of the database to 1 April 2022. CiteSpace 5.8.R3 (64-bit, Drexel University, Philadelphia, PA, USA) and Online Analysis Platform of Literature Metrology (https://bibliometric.com/) were used to perform bibliometric and knowledge-map analyses. Results: A total of 534 papers were included in 200 academic journals by 2,783 authors in 279 institutions from 50 countries/regions. The journal Cytokine published the most papers on IL-37, while Nature Immunology was the most co-cited journal. The publications belonged mainly to two categories of Immunology and Cell Biology. USA and China were the most productive countries. Meanwhile, the University of Colorado Denver in USA produced the highest number of publications followed by Radboud University Nijmegen in the Netherlands and Monash University in Australia. Charles A. Dinarello published the most papers, while Marcel F. Nold had the most co-citations. Top 10 co-citations on reviews, mechanisms, and diseases were regarded as the knowledge base. The keyword co-occurrence and co-citations of references revealed that the mechanisms and immune-related disorders were the main aspects of IL-37 research. Notably, the involvement of IL-37 in various disorders and the additional immunomodulatory mechanisms were two emerging hotspots in IL-37 research. Conclusions: The research on IL-37 was thoroughly reviewed using bibliometrics and knowledge-map analyses. The present study is a benefit for academics to master the dynamic evolution of IL-37 and point out the direction for future research. [ABSTRACT FROM AUTHOR]

Commensal bacteria and other microorganisms that reside in the human body are closely associated with the development and treatment of cancers. Recently, tumor microbiome (TM) has been identified in a variety of cancers such as pancreatic, lung, and breast cancers. TM has different compositions in different tumors and has different effects on tumors. TM plays an important role in the formation of the tumor microenvironment, regulation of local immunity, and modification of tumor cell biology, and directly affects the efficacy of drug treatment for tumors. TM is expected to be a biomarker for tumors, and engineered tumor-targeting bacteria and anti-cancer microbial agents (GEN-001) have an important role in the treatment of tumors. This paper reviews the relevant studies on TM in recent years and describes its distribution in different tumors, its correlation with clinical features, its effect on local immunity, and the research directions of TM in tumor treatment. [ABSTRACT FROM AUTHOR]

Gut microbiota is a microecosystem composed of various microorganisms. It plays an important role in human metabolism, and its metabolites affect different tissues and organs. Intestinal flora maintains the intestinal mucosal barrier and interacts with the immune system. The liver is closely linked to the intestine by the gut-liver axis. As the first organ that comes into contact with blood from the intestine, the liver will be deeply influenced by the gut microbiota and its metabolites, and the intestinal leakage and the imbalance of the flora are the trigger of the pathological reaction of the liver. In this paper, we discuss the role of gut microbiota and its metabolites in the pathogenesis and development of autoimmune liver diseases((including autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis), metabolic liver disease such as nonalcoholic fatty liver disease, cirrhosisits and its complications, and liver cancer from the perspective of immune mechanism. And the recent progress in the treatment of these diseases was reviewed from the perspective of gut microbiota. [ABSTRACT FROM AUTHOR]

An effective acute inflammatory response results in the elimination of infectious microorganisms, followed by a smooth transition to resolution and repair. During the inflammatory response, neutrophils play a crucial role in antimicrobial defense as the first cells to reach the site of infection damage. However, if the neutrophils that have performed the bactericidal effect are not removed in time, the inflammatory response will not be able to subside. Anti-inflammatory macrophages are the main scavengers of neutrophils and can promote inflammation towards resolution. MicroRNAs (miRNAs) have great potential as clinical targeted therapy and have attracted much attention in recent years. This paper summarizes the involvement of miRNAs in the process of chronic diseases such as atherosclerosis, rheumatoid arthritis and systemic lupus erythematosus by regulating lipid metabolism, cytokine secretion, inflammatory factor synthesis and tissue repair in two types of cells. This will provide a certain reference for miRNA-targeted treatment of chronic diseases. [ABSTRACT FROM AUTHOR]

Background: Immune system conditions of the patient is a key factor in COVID-19 infection survival. A growing number of studies have focused on immunological determinants to develop better biomarkers for therapies. Aim: Studies of the insurgence of immunity is at the core of both SARS-CoV-2 vaccine development and therapies. This paper attempts to describe the insurgence (and the span) of immunity in COVID-19 at the population level by developing an in-silico model. We simulate the immune response to SARS-CoV-2 and analyze the impact of infecting viral load, affinity to the ACE2 receptor, and age in an artificially infected population on the course of the disease. Methods: We use a stochastic agent-based immune simulation platform to construct a virtual cohort of infected individuals with age-dependent varying degrees of immune competence. We use a parameter set to reproduce known inter-patient variability and general epidemiological statistics. Results: By assuming the viremia at day 30 of the infection to be the proxy for lethality, we reproduce in-silico several clinical observations and identify critical factors in the statistical evolution of the infection. In particular, we evidence the importance of the humoral response over the cytotoxic response and find that the antibody titers measured after day 25 from the infection are a prognostic factor for determining the clinical outcome of the infection. Our modeling framework uses COVID-19 infection to demonstrate the actionable effectiveness of modeling the immune response at individual and population levels. The model developed can explain and interpret observed patterns of infection and makes verifiable temporal predictions. Within the limitations imposed by the simulated environment, this work proposes quantitatively that the great variability observed in the patient outcomes in real life can be the mere result of subtle variability in the infecting viral load and immune competence in the population. In this work, we exemplify how computational modeling of immune response provides an important view to discuss hypothesis and design new experiments, in particular paving the way to further investigations about the duration of vaccine-elicited immunity especially in the view of the blundering effect of immunosenescence. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum (ER) is an organelle equipped with mechanisms for proper protein folding, trafficking, and degradation to maintain protein homeostasis in the secretory pathway. As a defense mechanism, perturbation of ER proteostasis by ER stress agents activates a cascade of signaling pathways from the ER to the nucleus known as unfolded protein response (UPR). The primary goal of UPR is to induce transcriptional and translational programs to restore ER homeostasis for cell survival. As such, defects in UPR signaling have been implicated as a key contributor to multiple diseases including metabolic diseases, degenerative diseases, inflammatory disorders, and cancer. Growing evidence support the critical role of ER stress in regulating the fate as well as the magnitude of the immune response. Moreover, the availability of multiple UPR pharmacological inhibitors raises the hope that targeting UPR can be a new strategy for immune modulation and immunotherapy of diseases. This paper reviews the principal mechanisms by which ER stress affects immune cell biology and function, with a focus of discussion on UPR-associated immunopathology and the development of potential ER stress-targeted therapeutics., (Copyright © 2020 Li, Song, Riesenberg and Li.)

Winning the game "Rock, Scissors, Paper" depends on what others do. There is no guarantee that one choice will always win. Does the adaptive immune system use the same intransitive logic to select winners? Here I propose that specialized receptor-ligand pairs, called clicks, initiate contextual cell death to select the best adaptive immune response to a particular challenge. The outcome depends heavily on the phenotypic plasticity of the immune system and upon cell assemblies built from different lineages. These assemblies are self-organizing and use clicks to determine the combination of cells best equipped to defeat a threat. The arrangement is highly adaptive and capable of rapid evolution. Opportunities exist to re-engineer click-based assemblies to produce novel therapeutics. [ABSTRACT FROM AUTHOR]

In the present review, we focused on recent translational and clinical discoveries in asthma immunology, facilitating phenotyping and stratified or personalized interventions for patients with this condition. The immune processes behind chronic inflammation in asthma exhibit marked heterogeneity, with diverse phenotypes defining discernible features and endotypes illuminating the underlying molecular mechanisms. In particular, two primary endotypes of asthma have been identified: "type 2-high," characterized by increased eosinophil levels in the airways and sputum of patients, and "type 2-low," distinguished by increased neutrophils or a pauci-granulocytic profile. Our review encompasses significant advances in both innate and adaptive immunities, with emphasis on the key cellular and molecular mediators, and delves into innovative biological and targeted therapies for all the asthma endotypes. Recognizing that the immunopathology of asthma is dynamic and continuous, exhibiting spatial and temporal variabilities, is the central theme of this review. This complexity is underscored through the innumerable interactions involved, rather than being driven by a single predominant factor. Integrated efforts to improve our understanding of the pathophysiological characteristics of asthma indicate a trend toward an approach based on disease biology, encompassing the combined examination of the clinical, cellular, and molecular dimensions of the disease to more accurately correlate clinical traits with specific disease mechanisms. [ABSTRACT FROM AUTHOR]

Astaxanthin is an important aquatic feed additive that enhances the antioxidant capacity, and immune function of rainbow trout (Oncorhynchus mykiss); however, very limited information is available on its underlying molecular mechanisms. Haematococcus pluvialis powder, Phaffia rhodozyma powder, and synthetic astaxanthin were added to the commercial feed (no astaxanthin, NA) to prepare three experimental feeds, referred to as the HPA, PRA, and SA groups, respectively, and their actual astaxanthin contents were 31.25, 32.96, and 31.50 mg.kg-1, respectively. A 16-week feeding trial was conducted on the O. mykiss with an initial body weight of 669.88 ± 36.22 g. Serum and head kidney samples from commercial-sized O. mykiss were collected for metabolomics and transcriptomics analysis, respectively. Metabolomics analysis of the serum revealed a total of 85 differential metabolites between the astaxanthinsupplemented group and the control group. These metabolites were involved in more than 30 metabolic pathways, such as glycerophospholipid metabolism, fatty acid biosynthesis, linoleic acid metabolism, and arginine and proline metabolism. It is speculated that different sources of dietary astaxanthin may regulate antioxidant capacity and immunity mainly by affecting lipid metabolism and amino acid metabolism. Transcriptomic analysis of the head kidney revealed that the differentially expressed genes between the astaxanthin-supplemented group and the control group, such as integrin beta-1 (ITGB1), alpha-2-macroglobulin (A2M), diamine acetyltransferase 1 (SAT1), CCAAT/enhancer-binding protein beta (CEBPB) and DNA damage-inducible protein 45 alpha (GADD45A), which are involved in cell adhesion molecules, the FoxO signaling pathway, phagosomes, and arginine and proline metabolism and play regulatory roles in different stages of the antioxidant and immune response of O. mykiss. [ABSTRACT FROM AUTHOR]

Connective tissue diseases-related pulmonary arterial hypertension (CTD-PAH) is a disease characterized by an elevated pulmonary artery pressure that arises as a complication of connective tissue diseases. The number of patients with CTD-PAH accounts for 25.3% of all PAH patients. The main pathological features of CTD-PAH are thickening of intima, media and adventitia of pulmonary arterioles, increased pulmonary vascular resistance, autoimmune activation and inflammatory reaction. It is worth noting that abnormal immune activation will produce autoantibodies and release cytokines, and abnormal immune cell recruitment will promote inflammatory environment and vascular remodeling. Therefore, almost all forms of connective tissue diseases are related to PAH. In addition to general therapy and targeted drug therapy for PAH, high-dose glucocorticoid combined with immunosuppressant can quickly alleviate and stabilize the basic CTD-PAH disease. Given this, the development of therapeutic approaches targeting immune dysregulation and heightened inflammation is recognized as a promising strategy to prevent or reverse the progression of CTD-PAH. This review explores the potential mechanisms by which immune cells contribute to the development of CTD-PAH and examines the clinical application of immunosuppressive therapies in managing CTD-PAH. [ABSTRACT FROM AUTHOR]

Introduction: Leprosy is a chronic infectious condition and the main cause of neuropathy that occurs brought on by M. leprae. It is known that the biological characteristics of the human host, such as the immunological ones, have a higher influence on the pathology of this disease than the intrinsic mechanisms of the bacterium. The objective of this work was to review the scientific knowledge about the relationship between immunopathology and the severity of leprosy. Methods: A systematic review following the PRISMA 2020 recommendations was conducted in the PUBMED, LILACS, SciELO and Science Direct databases using articles in English, Portuguese or Spanish between January 2011 and May 2022 with the descriptors "Leprosy/Immunology", "Cytokines" and "Mycobacterium leprae". A methodological quality assessment was carried out using the JBI checklists. Results: A total of 49 articles were included. There is a relationship of greater severity of infection associated with lower release of MHC molecules in response to PGL-1 that inhibit the promotion of resolving T lymphocytes arising from dendritic cells (DCs) stimulation. In addition, the differentiation of macrophage phenotypes dependent on the activation of PRRs can define activation and the distinct type of T helper (Th) cells involved according to severity. Activated CD8+ T cells also have distinct types at the appropriate poles of the disease, and B cells show at the most severe pole of the LL, specific induction of IgA and more Treg-type CD8+ T cells that further contribute to T cell anergy. Conclusion: Therefore, the adaptive immune system aggravates nerve damage and defines the type of leprosy, while the innate immune system is considerably more significant in the onset of nerve damage, symptomatic of the initial presentation of illness and in several critical immune responses, including inflammation and elimination of dead M. leprae. [ABSTRACT FROM AUTHOR]

Despite the early recognition of obesity as an epidemic with global implications, research on its pathogenesis and therapeutic approach is still on the rise. The literature of the 21st century records an excess weight found in up to 1/3 of children. Both the determining factors and its systemic effects are multiple and variable. Regarding its involvement in the potentiation of cardio-vascular, pulmonary, digestive, metabolic, neuro-psychic or even dermatological diseases, the information is already broadly outlined. The connection between the underlying disease and the associated comorbidities seems to be partially attributable to oxidative stress. In addition to these, and in the light of the recent COVID-19 pandemic, the role played by oxidative stress in the induction, maintenance and potentiation of chronic inflammation among overweight children and adolescents becomes a topic of interest again. Thus, this review's purpose is to update general data on obesity, with an emphasis on the physiopathological mechanisms that underlie it and involve oxidative stress. At the same time, we briefly present the latest principles of pathology diagnosis and management. Among these, we will mainly emphasize the impact played by endogenous and exogenous antioxidants in the evolutionary course of pediatric obesity. In order to achieve our objectives, we will refer to the most recent studies published in the specialized literature. [ABSTRACT FROM AUTHOR]

In this review we give an update on the mechanisms of naturally acquired immunity against Streptococcus pneumoniae , one of the major human bacterial pathogens that is a common cause of pneumonia, septicaemia, and meningitis. A clear understanding of the natural mechanisms of immunity to S. pneumoniae is necessary to help define why the very young and elderly are at high risk of disease, and for devising new prevention strategies. Recent data has shown that nasopharynx colonization by S. pneumoniae induces antibody responses to protein and capsular antigens in both mice and humans, and also induces Th17 CD4+ cellular immune responses in mice and increases pre-existing responses in humans. These responses are protective, demonstrating that colonization is an immunizing event. We discuss the data from animal models and humans on the relative importance of naturally acquired antibody and Th17 cells on immunity to S. pneumoniae at three different anatomical sites of infection, the nasopharynx (the site of natural asymptomatic carriage), the lung (site of pneumonia), and the blood (site of sepsis). Mouse data suggest that CD4+ Th17 cells prevent both primary and secondary nasopharyngeal carriage with no role for antibody induced by previous colonization. In contrast, antibody is necessary for prevention of sepsis but CD4+ cellular responses are not. Protection against pneumonia requires a combination of both antibody and Th17 cells, in both cases targeting protein rather than capsular antigen. Proof of which immune component prevents human infection is less easily available, but two recent papers demonstrate that human IgG targeting S. pneumoniae protein antigens is highly protective against septicaemia. The role of CD4+ responses to prior nasopharyngeal colonization for protective immunity in humans is unclear. The evidence that there is significant naturally-acquired immunity to S. pneumoniae independent of anti-capsular polysaccharide has clinical implications for the detection of subjects at risk of S. pneumoniae infections, and the data showing the importance of protein antigens as targets for antibody and Th17 mediated immunity should aid the development of new vaccine strategies. [ABSTRACT FROM AUTHOR]

Keywords: damage-associated molecular patterns; immunity; inflammation; innate; pattern-recognition EN damage-associated molecular patterns immunity inflammation innate pattern-recognition 1 6 6 02/02/22 20220201 NES 220201 "The I danger/injury model i " of Immunity, formulated twenty seven years ago, holds that the immune system does not care about self vs. nonself, but rather that cell stress/tissue injury are the critical features that initiate an immune response ([1], [2]). Of note, these findings provide the first evidence for the concept that DAMP-promoted initiation of inflammation and SAMP-driven inflammation resolution, aimed at restoring homeostasis upon stress and injury, is a universal, evolutionarily ancient phenomenon. The core of the danger/injury model suggests that injured/stressed cells generate "danger signals", also known as damage-associated molecular patterns (DAMPs) ([3], [4]), or "alarmins" ([5]), and that these DAMPs initiate both healing and immunity. It currently appears that all organisms on our planet use DAMPs to signal that cell stress and tissue injury have occurred, be it of sterile or infectious nature ([7], [8]). [Extracted from the article]

Background: The Prognostic Nutritional Index (PNI) has become an important predictive tool for assessing patients' nutritional status and immune competence. It is widely used in prognostic evaluations for various cancer patients. However, the prognostic relevance of the Prognostic Nutritional Index (PNI) in gastric or gastro-esophageal junction cancer patients (GC/GEJC) undergoing immune checkpoint inhibitors (ICIs) treatment remains unclear. This meta-analysis aimed to determine the prognostic impact of PNI in this specific patient cohort. Methods: We conducted a thorough literature search, covering prominent databases such as PubMed, Embase, Web of Science, SpringerLink, and the Cochrane Library. The search spanned from the inception of these databases up to December 5, 2023. Employing the 95% confidence interval and Hazard Ratio (HR), the study systematically evaluated the relationship between PNI and key prognostic indicators, including the objective remission rate (ORR), disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) in GC/GEJC patients undergoing ICI treatment. Results: Eight studies comprising 813 eligible patients were selected. With 7 studies consistently demonstrating superior Overall Survival (OS) in the high- Prognostic Nutritional Index (PNI) group compared to their low-PNI counterparts (HR 0.58, 95% CI: 0.47-0.71, P<0.001). Furthermore, the results derived from 6 studies pointed out that the significant correlation between he low-PNI and poorer progression-free survival (PFS) (HR 0.58, 95% CI: 0.47-0.71, P<0.001). Subgroup analyses were performed to validate the robustness of the results. In addition, we conducted a meta-analysis of three studies examining the correlation between PNI and objective response rate/disease control rate (ORR/DCR) and found that the ORR/DCR was significantly superior in the high PNI group (ORR: RR: 1.24, P=0.002; DCR: RR: 1.43, P=0.008). Conclusion: This meta-analysis indicates that the low-PNI in GC/GEJC patients undergoing ICI treatment is significantly linked to worse OS and PFS. Therefore, PNI can serve as a prognostic indicator of post-treatment outcomes in patients with GC receiving ICIs. Further prospective studies are required to assess the reliability of these findings. Systematic review registration: https://inplasy.com/, identifier INPLASY202450133. [ABSTRACT FROM AUTHOR]

This document is a summary of a collection of articles from the journal Frontiers in Immunology, focusing on the role of CD1- and MR1-restricted T cells in immunity and disease. The articles discuss various topics, including the repertoire of lipids associated with CD1 isoforms, the mechanisms of iNKT cell recognition of glycolipid antigens, and the heterogeneity of iNKT cells in different tissues. They also explore the potential of NKT cells as targets for immune therapies in inflammatory bowel disease and obesity-associated tissue inflammation. The articles provide insights into the functions and regulation of these T cell subsets and highlight their potential for the development of new immunotherapies. [Extracted from the article]

This article, titled "Editorial: Women in cancer immunity and immunotherapy," discusses the contributions and challenges faced by women scientists in the field of cancer immunity and immunotherapy. It highlights the achievements of women scientists throughout history and acknowledges the gender gap that still exists in the field. The article also presents several original research articles and reviews that focus on various aspects of cancer immunity and immunotherapy. Overall, the article aims to encourage more women to pursue careers in scientific research and contribute to the advancement of the field. [Extracted from the article]

Immunotherapy has revolutionized cancer treatment, with the anti-PD-1/PD-L1 axis therapy demonstrating significant clinical efficacy across various tumor types. However, it should be noted that this therapy is not universally effective for all PD-L1-positive patients, highlighting the need to expedite research on the second ligand of PD-1, known as Programmed Cell Death Receptor Ligand 2 (PD-L2). As an immune checkpoint molecule, PD-L2 was reported to be associated with patient's prognosis and plays a pivotal role in cancer cell immune escape. An in-depth understanding of the regulatory process of PDL2 expression may stratify patients to benefit from anti-PD-1 immunotherapy. Our review focuses on exploring PD-L2 expression in different tumors, its correlation with prognosis, regulatory factors, and the interplay between PDL2 and tumor treatment, which may provide a notable avenue in developing immune combination therapy and improving the clinical efficacy of anti-PD-1 therapies. [ABSTRACT FROM AUTHOR]

Tumors pose a significant global public health challenge, resulting in numerous fatalities annually. CD8+ T cells play a crucial role in combating tumors; however, their effectiveness is compromised by the tumor itself and the tumor microenvironment (TME), resulting in reduced efficacy of immunotherapy. In this dynamic interplay, extracellular vesicles (EVs) have emerged as pivotal mediators, facilitating direct and indirect communication between tumors and CD8+ T cells. In this article, we provide an overview of how tumor-derived EVs directly regulate CD8+ T cell function by carrying bioactive molecules they carry internally and on their surface. Simultaneously, these EVs modulate the TME, indirectly influencing the efficiency of CD8+ T cell responses. Furthermore, EVs derived from CD8+ T cells exhibit a dual role: they promote tumor immune evasion while also enhancing antitumor activity. Finally, we briefly discuss current prevailing approaches that utilize functionalized EVs based on tumor-targeted therapy and tumor immunotherapy. These approaches aim to present novel perspectives for EV-based tumor treatment strategies, demonstrating potential for advancements in the field. [ABSTRACT FROM AUTHOR]

oncolytic peptide with potent anticancer activity but limited toxicity for non-malignant cells. LTX-315 induces both immunogenic tumor cell death and generation of tumor-specific immune responses in multiple experimental tumor models. Given the central role of dendritic cell (DC) maturation in the induction of antigen-specific immunity, we investigated the effect of LTX-315 treatment on the maturation of tumor-infiltrating DCs (TiDCs) and the generation of anti-melanoma immunity. We found that LTX-315 treatment induces the maturation of DCs, both indirectly through the release of cancer cell-derived damage-associated molecular patterns (DAMPs)/alarmins and nucleic acids (DNA and RNA) capable of triggering distinct Toll-like receptor (TLR) signaling, and, directly by activating TLR7. The latter results in the ignition of multiple intracellular signaling pathways that promotes DC maturation, including NF-kB, mitogen activated protein kinases (MAPKs), and inflammasome signaling, as well as increased type 1 interferon production. Critically, the effects of LTX-315 on DCs the consequent promotion of anti-melanoma immunity depend on the cytosolic signal transducer myeloid differentiation response gene 88 (MyD88). These results cast light on the mechanisms by which LTX-315 induces DC maturation and hence elicits anticancer immunity, with important implications for the use of LTX-315 as an anticancer immunotherapeutic. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 vaccination in rheumatoid arthritis (RA) patients treated with B cell-depleting drugs induced limited seroconversion but robust cellular response. We aimed to document specific T and B cell immunity in response to vaccine booster doses and breakthrough infection (BTI). Methods: We included 76 RA patients treated with rituximab who received up to four SARS-CoV-2 vaccine doses or three doses plus BTI, in addition to vaccinated healthy donors (HD) and control patients treated with tumor necrosis factor inhibitor (TNFi). We quantified anti-SARS-CoV-2 receptor-binding domain (RBD) Spike IgG, anti-nucleocapsid (NC) IgG, 92 circulating inflammatory proteins, Spike-binding B cells, and Spike-specific T cells along with comprehensive high-dimensional phenotyping and functional assays. Findings: The time since the last rituximab infusion, persistent inflammation, and age were associated with the anti-SARS-CoV-2 RBD IgG seroconversion. The vaccine-elicited serological response was accompanied by an incomplete induction of peripheral Spike-specific memory B cells but occurred independently of T cell responses. Vaccine- and BTI-elicited cellular immunity was similar between RA and HD ex vivo in terms of frequency or phenotype of Spike-specific cytotoxic T cells and in vitro in terms of the functionality and differentiation profile of Spike-specific T cells. Interpretation: SARS-CoV-2 vaccination in RA can induce persistent effector T-cell responses that are reactivated by BTI. Paused rituximab medication allowed serological responses after a booster dose (D4), especially in RA with lower inflammation, enabling efficient humoral and cellular immunity after BTI, and contributed overall to the development of potential durable immunity. [ABSTRACT FROM AUTHOR]

Introduction: One of the unexpected outcomes of the COVID-19 pandemic was the relatively low levels of morbidity and mortality in Africa compared to the rest of the world. Nigeria, Africa's most populous nation, accounted for less than 0.01% of the global COVID-19 fatalities. The factors responsible for Nigeria's relatively low loss of life due to COVID-19 are unknown. Also, the correlates of protective immunity to SARS-CoV-2 and the impact of pre-existing immunity on the outcome of the COVID-19 pandemic in Africa are yet to be elucidated. Here, we evaluated the natural and vaccine-induced immune responses from vaccinated, non-vaccinated and convalescent individuals in Southern Nigeria throughout the three waves of the COVID-19 pandemic in Nigeria. We also examined the pre-existing immune responses to SARS-CoV-2 from samples collected prior to the COVID-19 pandemic. Methods: We used spike RBD and N-IgG antibody ELISA to measure binding antibody responses, SARS-CoV-2 pseudotype assay protocol expressing the spike protein of different variants (D614G, Delta, Beta, Omicron BA1) to measure neutralizing antibody responses and nucleoprotein (N) and spike (S1, S2) direct ex vivo interferon gamma (IFNγ) T cell ELISpot to measure T cell responses. Result: Our study demonstrated a similar magnitude of both binding (N-IgG (74% and 62%), S-RBD IgG (70% and 53%) and neutralizing (D614G (49% and 29%), Delta (56% and 47%), Beta (48% and 24%), Omicron BA1 (41% and 21%)) antibody responses from symptomatic and asymptomatic survivors in Nigeria. A similar magnitude was also seen among vaccinated participants. Interestingly, we revealed the presence of preexisting binding antibodies (N-IgG (60%) and S-RBD IgG (44%)) but no neutralizing antibodies from samples collected prior to the pandemic. Discussion: These findings revealed that both vaccinated, non-vaccinated and convalescent individuals in Southern Nigeria make similar magnitude of both binding and cross-reactive neutralizing antibody responses. It supported the presence of preexisting binding antibody responses among some Nigerians prior to the COVID-19 pandemic. Lastly, hybrid immunity and heterologous vaccine boosting induced the strongest binding and broadly neutralizing antibody responses compared to vaccine or infection-acquired immunity alone. [ABSTRACT FROM AUTHOR]

This document is an editorial from the journal Frontiers in Immunology, titled "Community series in tumor ablation and immunity, volume II." The editorial discusses the use of tumor ablation therapy, which involves locally destroying tumors using advanced medical equipment. The therapy has been widely used in clinical practice due to its minimal invasiveness and high local therapeutic effects. The editorial highlights the relationship between tumor ablation and immunity, and the potential synergistic effects of combining ablation therapy with immunotherapy. It summarizes several studies published in the journal that explore different combinations of ablation therapy and immune checkpoint inhibitors, as well as other treatments such as electrochemotherapy and irreversible electroporation. The editorial concludes by emphasizing the need for further research to explore the potential of integrating tumor ablation and immunotherapy for more effective cancer treatment. [Extracted from the article]

This editorial, published in the journal Frontiers in Immunology, discusses the role of resident memory T cells (TRM) in maintaining local immunity and preventing pathology. It emphasizes the need to understand the dynamic control of TRM to improve clinical outcomes in cancer, infections, allergies, and autoimmune diseases. The document provides recommended articles for further reading and briefly mentions three specific studies related to T cell function in cancer, non-small cell lung cancer, and the role of IL-7 in T cell biology. It explores various research topics related to T cell responses and immunology, including measuring resting antigen-specific memory T cells as a method for monitoring diseases, the functions of granzyme C in T cells in the skin, the importance of respiratory tract immunization for establishing CD8+ TRM, and the role of CD8 T cells in controlling the reactivation of latent cytomegalovirus in white adipose tissue. The authors express gratitude to contributors and readers and pay tribute to Dr. Toshinori Nakayama, a renowned immunologist who passed away. [Extracted from the article]

This article, titled "Editorial: Comprehensive profiling cancer immunity with multimodal approaches for clinical management," discusses the importance of using multimodal approaches to understand and manage cancer. The immune system plays a crucial role in cancer development and progression, and integrating data from various sources can provide a deeper understanding of cancer immunity. The article summarizes several studies published in this collection, including research on immune checkpoint inhibitors, the combination of stereotactic radiosurgery and immunotherapy, the use of Toripalimab in nasopharyngeal carcinoma, neoadjuvant tislelizumab combined with chemotherapy, a deep learning framework for predicting cancer-associated T cell receptors, and the relationship between tuberculosis and tumor incidence. The studies aim to enhance our understanding of cancer immunity and improve clinical management. [Extracted from the article]

Adoptive cellular immunotherapy as a new paradigm to treat cancers is exemplified by the FDA approval of six chimeric antigen receptor-T cell therapies targeting hematological malignancies in recent years. Conventional αβ T cells applied in these therapies have proven efficacy but are confined almost exclusively to autologous use. When infused into patients with mismatched human leukocyte antigen, αβ T cells recognize tissues of such patients as foreign and elicit devastating graft-versus-host disease. Therefore, one way to overcome this challenge is to use naturally allogeneic immune cell types, such as γδ T cells. γδ T cells occupy the interface between innate and adaptive immunity and possess the capacity to detect a wide variety of ligands on transformed host cells. In this article, we review the fundamental biology of γδ T cells, including their subtypes, expression of ligands, contrasting roles in and association with cancer prognosis or survival, as well as discuss the gaps in knowledge pertaining to this cell type which we currently endeavor to elucidate. In addition, we propose how to harness the unique properties of γδ T cells for cellular immunotherapy based on lessons gleaned from past clinical trials and provide an update on ongoing trials involving these cells. Lastly, we elaborate strategies that have been tested or can be explored to improve the anti-tumor activity and durability of γδ T cells in vivo. [ABSTRACT FROM AUTHOR]

Mastitis, the inflammatory condition of mammary glands, has been closely associated with immune suppression and imbalances between antioxidants and free radicals in cattle. During the periparturient period, dairy cows experience negative energy balance (NEB) due to metabolic stress, leading to elevated oxidative stress and compromised immunity. The resulting abnormal regulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with increased non-esterified fatty acids (NEFA) and b-hydroxybutyric acid (BHBA) are the key factors associated with suppressed immunity thereby increases susceptibility of dairy cattle to infections, including mastitis. Metabolic diseases such as ketosis and hypocalcemia indirectly contribute to mastitis vulnerability, exacerbated by compromised immune function and exposure to physical injuries. Oxidative stress, arising from disrupted balance between ROS generation and antioxidant availability during pregnancy and calving, further contributes to mastitis susceptibility. Metabolic stress, marked by excessive lipid mobilization, exacerbates immune depression and oxidative stress. These factors collectively compromise animal health, productive efficiency, and udder health during periparturient phases. Numerous studies have investigated nutrition-based strategies to counter these challenges. Specifically, amino acids, trace minerals, and vitamins have emerged as crucial contributors to udder health. This review comprehensively examines their roles in promoting udder health during the periparturient phase. Trace minerals like copper, selenium, and calcium, as well as vitamins; have demonstrated significant impacts on immune regulation and antioxidant defense. Vitamin B12 and vitamin E have shown promise in improving metabolic function and reducing oxidative stress followed by enhanced immunity. Additionally, amino acids play a pivotal role in maintaining cellular oxidative balance through their involvement in vital biosynthesis pathways. In conclusion, addressing periparturient mastitis requires a holistic understanding of the interplay between metabolic stress, immune regulation, and oxidative balance. The supplementation of essential amino acids, trace minerals, and vitamins emerges as a promising avenue to enhance udder health and overall productivity during this critical phase. This comprehensive review underscores the potential of nutritional interventions in mitigating periparturient bovine mastitis and lays the foundation for future research in this domain. [ABSTRACT FROM AUTHOR]

Parasites reduce the fitness of their hosts, and different causes of this damage have fundamentally different consequences for the evolution of immune defences. Damage to the host may result from the parasite directly harming its host, often due to the production of virulence factors that manipulate host physiology. Alternatively, the host may be harmed by the activation of its own immune defences, as these can be energetically demanding or cause self-harm. A well-studied model of the cost of infection is Drosophila melanogaster and its common natural enemy, parasitoid wasps. Infected Drosophila larvae rely on humoral and cellular immune mechanisms to form a capsule around the parasitoid egg and kill it. Infection results in a developmental delay and reduced adult body size. To disentangle the effects of virulence factors and immune defences on these costs, we artificially activated anti-parasitoid immune defences in the absence of virulence factors. Despite immune activation triggering extensive differentiation and proliferation of immune cells together with hyperglycaemia, it did not result in a developmental delay or reduced body size. We conclude that the costs of infection do not result from these aspects of the immune response and may instead result from the parasite directly damaging the host. [ABSTRACT FROM AUTHOR]

As one of the deadliest cancers of the gastrointestinal tract, there has been limited improvement in long-term survival rates for gastric cancer (GC) in recent decades. The poor prognosis is attributed to difficulties in early detection, minimal opportunity for radical resection and resistance to chemotherapy and radiation. Macrophages are among the most abundant infiltrating immune cells in the GC stroma. These cells engage in crosstalk with cancer cells, adipocytes and other stromal cells to regulate metabolic, inflammatory and immune status, generating an immunosuppressive tumour microenvironment (TME) and ultimately promoting tumour initiation and progression. In this review, we summarise recent advances in our understanding of the origin of macrophages and their types and polarisation in cancer and provide an overview of the role of macrophages in GC carcinogenesis and development and their interaction with the GC immune microenvironment and flora. In addition, we explore the role of macrophages in preclinical and clinical trials on drug resistance and in treatment of GC to assess their potential therapeutic value in this disease. [ABSTRACT FROM AUTHOR]

Background: Cuproptosis, the most recently identified and regulated cell death, depends on copper ions in vivo. Copper regulates the pathogenesis of Idiopathic pulmonary fibrosis (IPF), but the mechanism of action underlying cuproptosis in IPF remains unclear. Methods: We identified three cuproptosis patterns based on ten cuproptosisrelated genes using unsupervised consensus clustering. We quantified these patterns using a PCA algorithm to construct a cuproptosis score. ssGSEA and the Cibersort algorithm assessed the immune profile of IPF patients. GSEA and GSVA were used to analyze the functional differences in different molecular patterns. Drug susceptibility prediction based on cuproptosis scores and meaningful gene markers was eventually screened in combination with external public data sets,in vitro experiments and our cases. Results: Of the three types of cuproptosis-related clusters identified in the study, patients in the clusterA, geneclusterB, and score-high groups showed improved prognoses. Moreover, each cluster exhibited differential immune characteristics, with the subtype showing a poorer prognosis associated with an immune overreaction. Cuproptosis score can be an independent risk factor for predicting the prognosis of IPF patients. GSEA showed a significant functional correlation between the score and cuproptosis. The genes AKAP9, ANK3, C6orf106, LYRM7, and MBNL1, were identified as prognostic-related signatures in IPF patients. The functional role of immune regulation in IPF was further explored by correlating essential genes with immune factors. Also, the nomogram constructed by cumulative information from gene markers and cuproptosis score showed reliable clinical application. Conclusions: Cuproptosis patterns differ significantly in the prognosis and immune characteristics of IPF patients. The cuproptosis score and five gene signatures can provide a reliable reference in the prognosis and diagnosis of IPF [ABSTRACT FROM AUTHOR]