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Skin cancer is one of the most widespread cancers, with a significant global health effect. UV-induced DNA damage in skin cells triggers them to grow and proliferate out of control, resulting in cancer development. Two common types of skin cancer include melanoma skin cancer (MSC) and non-melanoma skin cancer (NMSC). Melanoma is the most lethal form of skin cancer, and NMSC includes basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and other forms. The incidence of skin cancer is increasing in part owing to a demographic shift toward an aging population, which is more prone to NMSC, imposing a considerable financial strain on public health services. The introduction of immunostimulatory approaches for cancer cell eradication has led to significant improvements in skin cancer treatment. Over the last three decades, monoclonal antibodies have been used as powerful human therapeutics besides scientific tools, and along with the development of monoclonal antibody production and design procedures from chimeric to humanized and then fully human monoclonal antibodies more than 6 monoclonal antibodies have been approved by the food and drug administration (FDA) and have been successful in skin cancer treatment. In this review, we will discuss the epidemiology, immunology, and therapeutic approaches of different types of skin cancer.
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Beyond the encouraging results and broad clinical applicability of immune checkpoint (ICP) inhibitors in cancer therapy, ICP-based immunotherapies in the context of autoimmune disease, particularly multiple sclerosis (MS), have garnered considerable attention and hold great potential for developing effective therapeutic strategies. Given the well-established immunoregulatory role of ICPs in maintaining a balance between stimulatory and inhibitory signaling pathways to promote immune tolerance to self-antigens, a dysregulated expression pattern of ICPs has been observed in a significant proportion of patients with MS and its animal model called experimental autoimmune encephalomyelitis (EAE), which is associated with autoreactivity towards myelin and neurodegeneration. Consequently, there is a rationale for developing immunotherapeutic strategies to induce inhibitory ICPs while suppressing stimulatory ICPs, including engineering immune cells to overexpress ligands for inhibitory ICP receptors, such as program death-1 (PD-1), or designing fusion proteins, namely abatacept, to bind and inhibit the co-stimulatory pathways involved in overactivated T-cell mediated autoimmunity, and other strategies that will be discussed in-depth in the current review. Video Abstract.
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Encefalomielite Autoimune Experimental , Esclerose Múltipla , Animais , Humanos , Esclerose Múltipla/tratamento farmacológico , Encefalomielite Autoimune Experimental/terapia , Linfócitos T , Imunoterapia , AutoimunidadeRESUMO
BACKGROUND: Neutropenia is the most important cause of life-threatening invasive fungal infections (IFIs). Here, we studied the frequency and antifungal susceptibility profiles of Candida species that colonized or caused infections among neutropenic patients with solid or hematological malignancies. METHODS: A total of 362 clinical samples were collected from 138 patients. After initial isolation using a mix of mycological methods, isolates were screened using chromogenic culture media. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied for molecular identification. Positive or suspected cases were confirmed using the reference method of sequencing. Antifungal susceptibility testing for voriconazole and caspofungin was carried out using the microbroth dilution method. An in-silico assay was applied for phylogenetic analysis. RESULTS: Thirty-four Candida strains were isolated. C. albicans (47.06%) and C. glabrata (29.41%) were the most frequent strains. Antifungal treatment reduced the chance of Candida colonization by almost 76% in neutropenic patients (OR: 1.759; 95% CI: 1.349 to 2.390; p value: 0.000). An unusual and non-resistant strain, C. lambica, was reported from the bloodstream of a 56-year-old man with hematologic malignancy (HM). Eight isolates were non-susceptible, and one isolate was resistant to voriconazole. Also, four isolates were non-susceptible to caspofungin. CONCLUSION: We can conclude that there is a cause-and-effect relationship between neutropenia, HM background, and Candida species separated from neutropenic patients, which can lead to possible infections. Further and repetitive studies are recommended using different molecular methods for better prediction and management of fungal infections in neutropenic patients.
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Antifúngicos , Neutropenia , Humanos , Masculino , Pessoa de Meia-Idade , Antifúngicos/farmacologia , Candida , Candida albicans , Candida glabrata , Caspofungina , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Neutropenia/tratamento farmacológico , Filogenia , VoriconazolRESUMO
One of the most common diseases in the present era is cancer. The common treatment methods used to control cancer include surgery, chemotherapy, and radiotherapy. Despite progress in the treatment of cancers, there still is no definite therapeutic approach. Among the currently proposed strategies, immunotherapy is a new approach that can provide better outcomes compared with existing therapies. Employing natural killer (NK) cells is one of the means of immunotherapy. As innate lymphocytes, NK cells are capable of rapidly responding to cancer cells without being sensitized or restricted to the cognate antigen in advance, as compared to T cells that are tumor antigen-specific. Latest insights into the biology of NK cells have clarified the underlying molecular mechanisms of NK cell maturation and differentiation, as well as controlling their effector functions through the investigation of the ligands and receptors engaged in recognizing cancer cells by NK cells. Elucidating the fact that NK cells recognize cancer cells could similarly show the mechanism through which cancer cells possibly avoid NK cell-dependent immune surveillance. Additionally, the expectations for novel immunotherapies by targeting NK cells have increased through the latest clinical outcomes of T-cell-targeted cancer immunotherapy. For this emerging method, researchers are still attempting to develop protocols for conferring the best proliferation and expansion medium, activation pathways, utilization dosage, transferring methods, as well as reducing possible side effects in cancer therapy. This study reviews the NK cells, their proliferation and expansion methods, and their recent applications in cancer immunotherapy.
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Imunoterapia , Células Matadoras Naturais/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Humanos , Evasão da Resposta Imune/imunologia , Neoplasias/patologia , Receptores de Antígenos Quiméricos/metabolismoRESUMO
Osteosarcoma (OS) is one of the most common bone tumors in children and adolescents that cause a high rate of mortality in this age group and tends to be metastatic, in spite of chemotherapy and surgery. The main reason for this can be returned to a small group of malignant cells called cancer stem cells (CSCs). OS-CSCs play a key role in the resistance to treatment and relapse and metastasis through self-renewal and differentiation abilities. In this review, we intend to go through the different aspects of this malignant disease, including the cancer stem cell-phenotype, methods for isolating CSCs, signaling pathways, and molecular markers in this disease, and drugs showing resistance in treatment efforts of OS.
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Neoplasias Ósseas/terapia , Células-Tronco Neoplásicas/fisiologia , Osteossarcoma/terapia , Transplante de Células-Tronco/métodos , Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , HumanosRESUMO
Rapid growth in nanotechnology toward the development of nanomedicine agents holds massive promise to improve therapeutic approaches against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multifunctionality. Nowadays, nanoparticles (NPs) have multiple applications in different branches of science. In recent years, NPs have repetitively been reported to play a significant role in modern medicine. They have been analyzed for different clinical applications, such as drug carriers, gene delivery to tumors, and contrast agents in imaging. A wide range of nanomaterials based on organic, inorganic, lipid, or glycan compounds, as well as on synthetic polymers has been utilized for the development and improvement of new cancer therapeutics. In this study, we discuss the role of NPs in treating cancer among different drug delivery methods for cancer therapy.
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Nanopartículas/química , Neoplasias/tratamento farmacológico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Nanomedicina/métodos , Polímeros/químicaRESUMO
Among the main promising systems to triggering therapeutic antitumor immunity is the blockade of immune checkpoints. Immune checkpoint pathways regulate the control and eradication of infections, malignancies, and resistance against a host of autoantigens. Initiation point of the immune response is T cells, which have a critical role in this pathway. As several immune checkpoints are initiated by ligand-receptor interactions, they can be freely blocked by antibodies or modulated by recombinant forms of ligands or receptors. Antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) were the first immunotherapeutics that achieved the US Food and Drug Administration approval. Preliminary clinical results with the blockers of additional immune checkpoint proteins, such as programmed cell death protein 1 (PD-1) indicate extensive and different chances to boost antitumor immunity with the objective of conferring permanent clinical effects. This study provides an overview of the immune checkpoint pathways, including CTLA-4, PD-1, lymphocyte activation gene 3, T-cell immunoglobulin and mucin domain 3, B7-H3, and diacylglycerol kinase α and implications of their inhibition in the cancer therapy.
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Antineoplásicos Imunológicos/uso terapêutico , Imunoterapia , Neoplasias/tratamento farmacológico , Receptores Imunológicos/efeitos dos fármacos , Animais , Antineoplásicos Imunológicos/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Humanos , Imunoterapia/efeitos adversos , Terapia de Alvo Molecular , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/patologia , Receptores Imunológicos/imunologia , Receptores Imunológicos/metabolismo , Transdução de Sinais , Microambiente TumoralRESUMO
Exosomes offer a new perspective on the biology of cancer with both diagnostic and therapeutic concepts. Due to the cell-to-cell association, exosomes are involved in the progression, metastasis, and therapeutic efficacy of the tumor. They can be isolated from blood and other body fluids to determine the disease progression in the body, including cancer growth. In addition to being reservoirs of biochemical markers of cancer, exomes can be designed to restore tumor immunity. Tumor exosomes interact with different cells in the tumor microenvironment to confer beneficial modulations, responsible for stromal activity, angiogenesis, increased vascular permeability, and immune evasion. Exosomes also contribute to the metastasis with the aim of epithelial transmission to the mesenchyme and the formation of premetastatic niches. Moreover, exosomes protect cells against the cytotoxic effects of chemotherapeutic drugs and prevent the transmission of chemotherapy resistance to adjacent cells. Therefore, exosomes are essential for many fatal cancer agents, and understanding their origins and role in cancer is important. In this article, we attempted to clarify the potential of exosomes for the application in cancer diagnosis and therapy.
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Exossomos/imunologia , Neoplasias/diagnóstico , Neoplasias/patologia , Microambiente Tumoral/imunologia , Animais , Biomarcadores Tumorais/análise , Progressão da Doença , Humanos , Metástase Neoplásica/patologiaRESUMO
Osteosarcoma (OS) is the most common primary malignant tumor of the bone with a strong tendency to early metastasis, and occurs in growing bones more commonly in children and adolescents. Considering the limited therapeutic methods and lack of 100% success of these methods, developing innovative therapies with high efficacy and lower side effects is needed. Meanwhile, miRNAs and the studies indicating the involvement of miRNAs in OS development have attracted attentions as a result of the frequent abnormalities in expression of miRNAs in cancer. miRNAs are noncoding short sequences with lengths ranging from 18 to 25 nucleotides that play a very important role in cellular processes, such as proliferation, differentiation, migration, and apoptosis. MiRNAs can have either oncogenic or tumor suppressive role based on cellular function and targets. This review aimed to have overview on miR-142 as a tumor suppressor in OS. Moreover, the genes involved in the disease, such as RAC1, HMAG1, MMP9, MMP2, and E-cadherin, which have irregularities as a result of change in miR-142 expression, and, thereby, result in increasing the proliferation, invasion, and metastasis of the cells in the tissues and OS cells will be discussed.
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Neoplasias Ósseas/genética , MicroRNAs/genética , Osteossarcoma/genética , Adolescente , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Criança , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , MicroRNAs/metabolismo , Osteossarcoma/metabolismo , Osteossarcoma/patologiaRESUMO
Bacteriophages are specific antagonists to bacterial hosts. These viral entities have attracted growing interest as optimal vaccine delivery vehicles. Phages are well-matched for vaccine design due to being highly stable under harsh environmental conditions, simple and inexpensive large scale production, and potent adjuvant capacities. Phage vaccines have efficient immunostimulatory effects and present a high safety profile because these viruses have made a constant relationship with the mammalian body during a long-standing evolutionary period. The birth of phage display technology has been a turning point in the development of phage-based vaccines. Phage display vaccines are made by expressing multiple copies of an antigen on the surface of immunogenic phage particles, thereby eliciting a powerful and effective immune response. Also, the ability to produce combinatorial peptide libraries with a highly diverse pool of randomized ligands has transformed phage display into a straightforward, versatile and high throughput screening methodology for the identification of potential vaccine candidates against different diseases in particular microbial infections. These libraries can be conveniently screened through an affinity selection-based strategy called biopanning against a wide variety of targets for the selection of mimotopes with high antigenicity and immunogenicity. Also, they can be panned against the antiserum of convalescent individuals to recognize novel peptidomimetics of pathogen-related epitopes. Phage display has represented enormous promise for finding new strategies of vaccine discovery and production and current breakthroughs promise a brilliant future for the development of different phage-based vaccine platforms.
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In the chronic, organ-specific autoimmune disorder known as multiple sclerosis (MS), the myelin sheath is attacked by immune cells, leading to damage to the central nervous system (CNS). It has been discovered that miRNAs are important in the etiology of MS, since deregulation of miRNAs can lead to defects in immune tolerance. In this study, we sought to investigate the involvement of miR-155 in MS disorder through examination of its altered expression in peripheral blood mononuclear cells (PBMCs) of patients with MS in compare with healthy controls. Furthermore, we investigated the frequency of T helper 17 cells (Th17) in MS patients and analyzed not only the expression of inflammatory cytokines including IL-6, IL-17 and IL-21 in patients' PBMCs, but also their secreted levels in serum of patients suffering from MS. Subsequently, we assessed the correlation between miR-155 expression with Th17 frequency and levels of released cytokines in serum. Upregulated expression of miR-155 was detected in PBMCs of MS patients and the positive correlation between its expression with increased frequency of Th17 cells and their related inflammatory cytokine profile augmented secretion in serum were identified. In conclusion, our study revealed the significant association between Th17 frequency, increased level of cytokines related to Th17 differentiation and function with miR-155 augmented expression in PBMCs. So, our findings suggested that miR-155 and especially its expression in immune cells including effector T cells can be the target of future therapeutic strategies for the management and prevention of MS progression, however, further research is requisite before this approach can be utilized in clinical practice.
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Glioblastoma multiform (GBM) is the most prevalent CNS (central nervous system) tumor in adults, with an average survival length shorter than 2 years and rare metastasis to organs other than CNS. Despite extensive attempts at surgical resecting, the inherently permeable nature of this disease has rendered relapse nearly unavoidable. Thus, immunotherapy is a feasible alternative, as stimulated immune cells can enter into the remote and inaccessible tumor cells. Immunotherapy has revolutionized patient upshots in various malignancies and might introduce different effective ways for GBM patients. Currently, researchers are exploring various immunotherapeutic strategies in patients with GBM to target both the innate and acquired immune responses. These approaches include reprogrammed tumor-associated macrophages, the use of specific antibodies to inhibit tumor progression and metastasis, modifying tumor-associated macrophages with antibodies, vaccines that utilize tumor-specific dendritic cells to activate anti-tumor T cells, immune checkpoint inhibitors, and enhanced T cells that function against tumor cells. Despite these findings, there is still room for improving the response faults of the many currently tested immunotherapies. This study aims to review the currently used immunotherapy approaches with their molecular mechanisms and clinical application in GBM.
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Neoplasias Encefálicas , Vacinas Anticâncer , Glioblastoma , Imunoterapia , Glioblastoma/terapia , Glioblastoma/imunologia , Humanos , Imunoterapia/métodos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/imunologia , Vacinas Anticâncer/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Células Dendríticas/imunologia , Macrófagos Associados a Tumor/imunologia , Linfócitos T/imunologiaRESUMO
The successful outcomes of chimeric antigen receptor (CAR) T-cell therapy in treating hematologic cancers have increased the previously unprecedented excitement to use this innovative approach in treating various forms of human cancers. Although researchers have put a lot of work into maximizing the effectiveness of these cells in the context of solid tumors, few studies have discussed challenges and potential strategies to overcome them. Restricted trafficking and infiltration into the tumor site, hypoxic and immunosuppressive tumor microenvironment (TME), antigen escape and heterogeneity, CAR T-cell exhaustion, and severe life-threatening toxicities are a few of the major obstacles facing CAR T-cells. CAR designs will need to go beyond the traditional architectures in order to get over these limitations and broaden their applicability to a larger range of malignancies. To enhance the safety, effectiveness, and applicability of this treatment modality, researchers are addressing the present challenges with a wide variety of engineering strategies as well as integrating several therapeutic tactics. In this study, we reviewed the antigens that CAR T-cells have been clinically trained to recognize, as well as counterstrategies to overcome the limitations of CAR T-cell therapy, such as recent advances in CAR T-cell engineering and the use of several therapies in combination to optimize their clinical efficacy in solid tumors.
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Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva , Antígenos de Neoplasias , Linfócitos T , Microambiente TumoralRESUMO
Although there exist manifold strategies for cancer treatment, researchers are obliged to develop novel treatments based on the challenges that arise. One of these recent treatment approaches is cancer immunotherapy, which enjoys various types of strategies itself. However, one of the most significant methods, in this regard, is employing immune checkpoint proteins (ICPs). Bone sarcomas have several subtypes, with the most common ones being chordoma, chondrosarcoma, Ewing sarcoma, and osteosarcoma. Although many aggressive treatment approaches, including radiotherapy, chemotherapy, and surgical resection, have been employed over the last decades, significantly improved outcomes have not been observed for Ewing sarcoma or osteosarcoma patients. Additionally, chordoma and chdrosarcoma resist against both radiation and chemotherapy. Accordingly, elucidating how recent therapies could affect bone sarcomas is necessary. Checkpoint inhibitors have attracted great attention for the treatment of several cancer types, including bone sarcoma. Herein, the recent advances of current immune checkpoint targets, such as anti-PD-1/PD-L1 and anti-CTLA-4 blockade, for the treatment of bone sarcoma have been reviewed.
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Currently, the significance of fungi as human pathogens is not medically concealed in the world. Consequently, suitable recognition and treatment of such infections are of great importance and necessitate the need for comprehensive information in this regard. The introduction of new antifungals and their use today, especially in the last two decades, have revolutionized the treatment of fungal infections. On the other hand, increasing drug resistance in the world has overshadowed such developments. The use of NPs results in the treatment of fungal infections and owing to their specific properties, these particles, unlike the pure antibiotics, can exert a greater inhibitory power although with less concentration compared with conventional drugs. Important reasons that have led to the use of antifungal drugs in delivery systems include reduced drug efficacy, limited penetration through tissue, poor aqueous solubility, decreased bioavailability, and poor drug pharmacokinetics. It is therefore hoped that unfavorable properties of antifungal drugs be mitigated via their incorporation into different types of NPs. This review summarizes the different types of NPs as delivery systems of antifungal as well as their advantages over pure drugs.
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Recent molecular investigations have significantly developed our knowledge of the characteristics of the reproductive microbiome and their associations with host responses to provide an ideal milieu for the development of the embryo during the peri-implantation period and throughout pregnancy as well as to provide a successful in vitro fertilization and appropriate reproductive outcomes. In this context, the establishment of microbial homeostasis in the female reproductive tract, in various physiological periods, is a substantial challenge, which appears the application of probiotics can facilitate the achievement of this goal. So that, currently, probiotics due to its safe and natural features can be considered as a novel biotherapeutic approach. In this review, we comprehensively discuss the bacterial, fungal, and viral diversity detected in the reproductive tract, and their associations with the establishment of dysbiosis/eubiosis conditions as well as we present the significant outcomes on probiotic intervention as an efficient biotherapeutic strategy for management of gestational disorders and improve pregnancy outcomes.
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Disbiose/dietoterapia , Genitália Feminina/microbiologia , Microbiota/imunologia , Complicações na Gravidez/dietoterapia , Probióticos/uso terapêutico , Suplementos Nutricionais , Disbiose/imunologia , Disbiose/microbiologia , Feminino , Genitália Feminina/imunologia , Humanos , Gravidez , Complicações na Gravidez/imunologia , Complicações na Gravidez/microbiologia , Resultado da GravidezRESUMO
Immune checkpoint pathways consist of stimulatory pathways, which can function like a strong impulse to promote T helper cells or killer CD8+ cells activation and proliferation. On the other hand, inhibitory pathways keep self-tolerance of the immune response. Increasing immunological activity by stimulating and blocking these signaling pathways are recognized as immune checkpoint therapies. Providing the best responses of CD8+ T cell needs the activation of T cell receptor along with the co-stimulation that is generated via stimulatory checkpoint pathways ligation including Inducible Co-Stimulator (ICOS), CD40, 4-1BB, GITR, and OX40. In cancer, programmed cell death receptor-1 (PD-1), Programmed cell death ligand-1(PD-L1) and Cytotoxic T Lymphocyte-Associated molecule-4 (CTLA-4) are the most known inhibitory checkpoint pathways, which can hinder the immune responses which have specifically anti-tumor characteristics and attenuate T cell activation and also cytokine production. The use of antagonistic monoclonal antibodies (mAbs) that block CTLA-4 or PD-1 activation is used in a variety of malignancies. It has been reported that they can lead to an increase in T cells and thereby strengthen anti-tumor immunity. Agonists of stimulatory checkpoint pathways can induce strong immunologic responses in metastatic patients; however, for achieving long-lasting benefits for the wide range of patients, efficient combinatorial therapies are required. In the present review, we focus on the preclinical and basic research on the molecular and cellular mechanisms by which immune checkpoint inhibitor blockade or other approaches with co-stimulatory agonists work together to improve T-cell antitumor immunity.
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As co-stimulatory receptors, immune checkpoint molecules are found on the surface of various immune cells and transduce inhibitory signals following ligand binding. The most studied members in this regard include PD-1, TIM-3, and CTLA-4. The physiological part immune checkpoints possess is the prevention of dangerous immune attacks towards self-antigens throughout an immune response, which takes place through the negative regulation of the effector immune cells, through the induction of T-cell exhaustion, for instance. It has recently been suggested that each checkpoint reduces immunoactivation via distinct intracellular mechanisms of signaling. Regulators of immune checkpoints are supposed to participate actively in immune defense mechanisms against infections, preventing autoimmunity, transplantation, and tumor immune evasion. In pregnancy, as an active immunotolerance mechanism which is also natural, the maternal immune system encounters two simultaneous challenges; in addition to accepting the semi-allogeneic fetus, the maternal immune system should also prevent infections. In this regard, the part immune checkpoint molecules possess is particularly interesting. Herein, the current understanding of such part in reproductive immunology is described.
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Biomarcadores/metabolismo , Antígeno CTLA-4/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Inibidores de Checkpoint Imunológico/metabolismo , Infertilidade/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Animais , Autoimunidade , Humanos , Tolerância Imunológica , Imunidade , Imunoterapia , Infertilidade/terapia , Ligantes , Neoplasias , Transdução de Sinais/imunologia , Evasão TumoralRESUMO
Human platelet lysate has attracted much interest from many researchers as it is growth-factor rich for cell expansion, which is employed as a new therapeutic strategy. Not only are human platelet lysates used for cell therapy, but they are also used for the completion of basal media in mesenchymal stem cell cultures. Due to the presence of a large number of growth factors, platelet lysates have potential roles in wound healing, treatment of ocular graft-versus-host disease, osteoarthritis, Parkinson's disease, tendon regeneration, infertility, androgenetic alopecia, nerve repair and regenerative tissue, such as bone regeneration. In this review, we summarize that platelet lysates could be valuable candidates for the treatment of a variety of diseases in regenerative medicine.