International Reviews of Immunology最新文献

The aggressive and recurrent nature of glioblastoma is multifactorial and has been attributed to its biological heterogeneity, dysfunctional metabolic signaling pathways, rigid blood-brain barrier, inherent resistance to standard therapy due to the stemness property of the gliomas cells, immunosuppressive tumor microenvironment, hypoxia and neoangiogenesis which are very well orchestrated and create the tumor's own highly pro-tumorigenic milieu. Once the relay of events starts amongst these components, eventually it becomes difficult to control the cascade using only the balanced contemporary care of treatment consisting of maximal resection, radiotherapy and chemotherapy with temozolamide. Over the past few decades, implementation of contemporary treatment modalities has shown benefit to some extent, but no significant overall survival benefit is achieved. Therefore, there is an unmet need for advanced multifaceted combinatorial strategies. Recent advances in molecular biology, development of innovative therapeutics and novel delivery platforms over the years has resulted in a paradigm shift in gliomas therapeutics. Decades of research has led to emergence of several treatment molecules, including immunotherapies such as immune checkpoint blockade, oncolytic virotherapy, adoptive cell therapy, nanoparticles, CED and BNCT, each with the unique proficiency to overcome the mentioned challenges, present research. Recent years are seeing innovative combinatorial strategies to overcome the multifactorial resistance put forth by the GBM cell and its TME. This review discusses the contemporary and the investigational combinatorial strategies being employed to treat GBM and summarizes the evidence accumulated till date.

Since B7-H3 is overexpressed or amplified in many types of solid tumors with a restricted expression in the normal tissues, it has been an emerging immunotherapeutic target for solid tumors. This review will focus on the structural designs of developing chimeric antigen receptors (CARs) targeting B7-H3. The expression, receptor, and function of the B7-H3, as well as a short overview of B7-H3-targeted monoclonal antibody therapy, are discussed. Finally, a detailed summary of B7-H3 redirected CAR-T and CAR-NK cell approaches utilized in preclinical models and currently ongoing or completed clinical trials are presented. It has been demonstrated that B7-H3-targeted CAR-based cell therapies were safe in initial trials, but their efficacy was limited. Employing the local delivery routes, the introduction of novel modifications promoting CAR-T persistence, and combined treatment with other standard therapies could improve the efficacy of B7-H3-targeted CAR-T cell therapy against solid tumors.

Several risk factors are known to be involved in the initiation and development of gastric cancer. Among them, H. pylori is one of the most prominent with multiple virulence factors contributing to its pathogenicity. In this study, we have discussed an interesting immunological cycle exploring the interplay between H. pylori, aryl hydrocarbon receptor (AHR), tryptophan, arginine, and the metabolites of these two amino acids in the development of gastric cancer. AHR is a ligand-activated transcription factor which acts as a regulator for a diverse set of genes and has various types of exogenous and endogenous ligands. The tryptophan metabolite, kynurenine, is one of these ligands that can interact with AHR, leading to immune suppression and subsequently, susceptibility to gastric cancer. On the other hand, H. pylori downregulates the expression of AHR and AHR repressor (AHRR), leading to increased inflammatory cytokine production. A metabolite of the kynurenine pathway, xanthurenic acid, is a potent inhibitor of a terminal enzyme in the synthetic pathway of tetrahydrobiopterin (BH4). BH4, itself, is a cofactor in the process of nitric oxide (NO) production from arginine that has been shown to have immune-enhancing properties. Arginine has also been evidenced to have anti-tumoral function through inducing apoptosis in gastric cell lines; however, controversy exists regarding the anti-tumor role of arginine and BH4, since they are also associated with increased NO production, subsequently promoting tumor angiogenesis. Hence, although several synergistic connections result in immunity improvement, these correlations can also act as a double-edged sword, promoting tumor development. This emphasizes on the need for further investigations to better understand this complex interplay.

Indoleamine 2, 3-dioxygenase (IDO) as an intracellular cytosolic enzyme converts tryptophan (Trp) to N-formyl kynurenine which leads to proinflammatory T-cell apoptosis and prevention of immune cells maturation via decreasing the level of cellular energy. Trp catabolism products such as kynurenine increase the recruitment of regulatory T cells and induce immune tolerance in dendritic cells. IDO expression can locally suppress immunity in the tumor microenvironment and tumor progression actively recruits IDO expressing cells in tumor-draining lymph nodes. Also, tumor infiltrating Tregs' activity leads to IDO expression in the tumor microenvironment. In this review, we described the immunomodulatory function of IDO and IDO-based therapeutic strategies for immune related diseases. According to positive-feedback loop between Tregs and IDO in the tumor microenvironment, IDO can be targeted as a promising immunostimulatory approach for immunotherapy of cancer. However, several studies revealed controversial consequences for influences of IDO in immunity. Considering the common concept, IDO1 and also IDO2 repress the function of T lymphocytes, while inactivation of IDO results in aggravation of some autoimmune diseases. Eventually, the extensive evaluation of IDO function in immunomodulatory procedure can help achieve IDO inhibitors as optimal drugs to inhibit tumor growth without motivating autoimmunity.

The immune system response of transplant recipients is the main cause of allograft rejection; therefore, its suppression seems crucial. Nevertheless, immunosuppressive agents are largely ineffective against innate immune response. Innate immunity is immediately activated after transplantation and contribute to allograft inflammation and rejection. In this regard, understanding the mechanism of activation and targeting the components of innate immunity could improve allograft survival time. In this review, we discuss two scenarios in the innate immunity, i.e., danger and allogeneic signals in the context of both allogeneic and syngeneic graft. Moreover, the mechanisms of innate allorecognition (i.e., signal regulatory protein α-CD47 and paired immunoglobulin-like receptors-MHC I axis) are described, which can improve our clinical decisions to use a better therapeutic strategy.

Vaccines for the prevention of coronavirus disease 2019 (COVID-19) started to be developed since the initiation of the COVID-19 pandemic. Up to now, four vaccines have been authorized by international agencies such as European Medicines Agency (EMA). Two are DNA vaccines (ChAdOx1 nCov-19 and Ad26.COV2.S) and two mRNA vaccines (BNT162b2 and mRNA-1273). The administration of the vaccines has been associated with a strong decrease in the infections by SARS-CoV-2 and deaths associated with it. However, in parallel to these results, some rare adverse events have also been described. In that sense, events of thrombosis, thrombocytopenia, and hemorrhage have been described in close temporal proximity to the administration of the DNA vaccines ChAdOx1 nCov-19 and Ad26.COV2.S, but also mRNA vaccines. Recent scientific reports have been released with updated information on the possible association of thrombotic thrombocytopenia and COVID-19 vaccines. On the other hand, since the initiation of the vaccination campaigns, adverse hypersensitivity reactions have been described after mRNA and DNA vaccines administration for COVID-19. Although globally these adverse events are rare, a high proportion of the world population will be exposed to these vaccines. For that reason, their safety and tolerance should be carefully considered. In this review, we provide an updated review of the last scientific findings that can explain the rare side effects that the vaccines for COVID-19 can produce.

Lipopolysaccharide (LPS) is the major component of the outer membrane of Gram-negative bacteria. It is found from intestinal microbes in the circulatory system and considered a trigger factor for low-grade inflammation in obesity. High-fat diet intake and its related obesity can cause gut microbiota disorder, leading to increased gut permeability, paracellular absorption and transcellular transport of endogenous endotoxin in the cardiovascular system. High-fat diet intake can also increase plasma LPS levels, and causing chronic or "low-grade" inflammation. In this review article, we summarize the recent research advancements on the mechanism of low-grade inflammation and its related obesity. We also propose several approaches that can be used to reduce endogenous endotoxin absorption.Supplemental data for this article is available online at https://doi.org/10.1080/08830185.2021.1996573 .

Immunological memory is critical for host immunity and decisive for individual to respond exponentially to previously encountered infection. Both T and B cell memory are known to orchestrate immunological memory with their central and effector memory arms contributing in prolonged immunity/defence mechanisms of host. While central memory helps in maintaining prolonged immunity for a particular infection, effector memory helps in keeping local/seasonal infection in control. In addition to this, generation of long-lived plasma cells is pivotal for generating neutralizing antibodies which can enhance recall and B cell memory to control re-infection. In view of this, scaling up memory response is one of the major objectives for the expected outcome of vaccination. In this line, this review deals with the significance of memory cells, molecular pathways of their development, maintenance, epigenetic regulation and negative regulation in various infections. We have also highlighted the significance of both T and B cell memory responses in the vaccination approaches against range of infections which is not fully explored so far.[Box: see text].

Bacillus Calmette-Guérin (BCG) is a live attenuated M. bovis vaccine that was developed about 100 years ago by Albert Calmette and Camille Guérin. Many countries have been using the vaccine for decades against tuberculosis (TB). The World Health Organization (WHO) recommends a single dose of BCG for infants in TB endemic as well as leprosy high risk countries, and globally almost 130 million infants are vaccinated yearly. The role of BCG is well known in reducing neonatal and childhood death rates. Epidemiological and retrospective cross-sectional studies demonstrated that the BCG vaccination protects the children against respiratory tract infections and lowers the risk of malaria in children. In addition, BCG enhances IFN-γ and IL-10 levels, thus providing immunity against respiratory tract infection even in elderly people. The BCG is also known to provide nonspecific innate immunity against viruses and parasites, through an innate immune mechanism termed 'trained immunity' and is defined as the immunological recall of the innate immune system by epigenetic reprogramming. Based on these studies it is suggested that the BCG has the potential to act as a protective agent against COVID-19. Further proven safety records of BCG in humans, its adjuvant activity and low-cost manufacturing make it an attractive option to stop the pandemic and reduce the COVID-19 related mortality. In this review we discuss the heterologous effects of BCG, induction of trained immunity and its implication in development of a potential vaccine against COVID-19 pandemic.