BACKGROUND: We previously reported that preoperative chemoradiotherapy (CRT) combined with intraoperative electron irradiation for cT3/T4 adenocarcinoma of the rectum reduced the local recurrence, with significant improvement of survival. Radiotherapy has been reported to reduce immune function. We examined the effects of PSK, a protein-bound polysaccharide, concomitant with preoperative CRT on ...

A number of studies have shown that melanoma is a particularly immunogenic tumour, at least in the early stages of its development. A range of clinical phenomena also suggests that immune responses play an important role in the natural history of the disease, including the total or partial regression of ...

In the present study, the water-soluble polysaccharides of Radix Aconiti, Radix Aconiti Lateralis and Radix Aconiti Kusnezoffii, were extracted and fractionated into four fractions of each material. The FT-IR and chemical analyses indicated the water-soluble polysaccharides of the three materials were all mainly composed of starch, non-starch type alpha-D-glucans and ...

BACKGROUND: Considering the high mortality rate of ovarian cancer due to the absence of curative treatment in advanced stage or at recurrence, new therapeutic strategies are urgently needed. Immunotherapy is one of these strategies that yielded promising results in fundamental and animal research in the past years. However, implementation in ...

The success of active immunotherapy is based on the vaccine's ability to overcome immune tolerance through recalibrating the immune system so that it is able to recognize tumor antigens as foreign rather than self. In this study, we used a lentiviral vector system to target human telomerase reverse transcriptase (lv-hTERT), ...

The broad antimicrobial and antitumoral reactivity of Vgamma9Vdelta2 T cells, their ability to produce inflammatory cytokines involved in protective immunity against intracellular pathogens and tumors and their strong cytolytic and bactericidal activities suggest their direct involvement in immune control of cancers and infections. gammadelta T cells can be selectively activated ...

Most protein therapeutics have the potential to induce undesirable immune responses in patients. Many patients develop anti-therapeutic antibodies, which can affect the safety and efficacy of the therapeutic protein, particularly if the response is neutralizing. There are a variety of factors that influence the immunogenicity of protein therapeutics and, in ...

By destroying tumor cells, conventional anticancer therapies may stimulate the host immune system to eliminate residual disease. Anthracyclines, oxaliplatin, and ionizing irradiation activate a type of tumor cell death that elicits efficient anticancer immune responses depending on interferon gamma (IFNgamma) and the IFNgamma receptor. Thus, dying tumor cells emit danger ...

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are indispensable factors in the body's ongoing defence against viral infection and tumor development. CTL/NK cells recognize and kill infected or aberrant target cells by two major pathways: either through introduction of a battery of proteases - called granzymes - to ...

Human metapneumovirus (hMPV) is a major cause of upper and lower respiratory-tract infection in infants, the elderly and immunocompromised individuals. Virus-directed cellular immunity elicited by hMPV infection is poorly understood, in contrast to the phylogenetically and clinically related pathogen human respiratory syncytial virus (hRSV). In a murine model of acute ...

The simian immunodeficiency virus- (SIV-) infected rhesus macaque is the preferred animal model for vaccine development, but the correlates of protection in this model are not completely understood. In this paper, we document the cytotoxic T lymphocyte (CTL) response to SIV and its effects on viral evolution in an effort ...

Cytotoxic T lymphocytes (CTLs) play a crucial role in the infections and the antitumor immunity. Induction and activation of antigen-specific CTLs is an important strategy in immunotherapy for various diseases, and several researchers have focused on the modulation of CTL induction and function. Natural killer T (NKT) cells are an ...

Immune fitness is critical in the pathogenesis and outcome of cytomegalovirus (CMV) infection. CMV disease is seen almost exclusively among individuals with an immature or defective immune system, such as patients with AIDS, transplant recipients and the developing fetus. These observations have generated interest in immune-based strategies for the management ...

Lymphomas represent a wide group of heterogenic diseases with different biological and clinical behavior. The underlying microenvironment-specific composition seems to play an essential role in this scenario, harboring the ability to develop successful immune responses or, on the contrary, leading to immune evasion and even promotion of tumor growth. Depending ...

The ability of the tumor necrosis factor receptor (TNFR) family member GITR to modulate immune responses has been the subject of multiple studies. Initially thought to be critically involved in governing functions of regulatory T cells, GITR and its ligand GITRL have meanwhile been found to modulate the reactivity of ...

Abnormalities of cellular immunity are commonly seen in patients with glioblastoma (GBM), and the subsequent relative immunosuppression likely contributes to poor tumor-specific responses in affected individuals. Endogenous immune regulation is likely to limit the efficacy of a wide array of immunotherapeutic strategies, therefore mandating consideration in the continued development of ...

Several immunostimulant approaches have been studied in the treatment of gliomas. The advent of recombinant DNA technology led to a nonspecific immunostimulation via systemic administration of cytokines. Recently, in attempts to more closely mimic their natural activity, cytokines have been delivered by implanting genetically transduced cells or by using in ...

Despite advances in understanding the molecular mechanisms of brain cancer, the outcome of patients with malignant gliomas treated according to the current standard of care remains poor. Novel therapies are needed, and immunotherapy has emerged with great promise. The diffuse infiltration of malignant gliomas is a major challenge to effective ...

Numerous in vitro studies have shown that toll-like receptor signaling induces 25-hydroxyvitamin D(3) 1α-hydroxylase (1α-OHase; CYP27B1) expression in macrophages from various species. 1α-OHase is the primary enzyme that converts 25-hydroxyvitamin D(3) to 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Subsequently, synthesis of 1,25(OH)(2)D(3) by 1α-OHase in macrophages has been shown to modulate innate immune ...

Adoptive transfer of specific cytotoxic T lymphocytes (CTL) and Cytokine Induced Killer Cells (CIK) following genetic engineering of T-cell receptor zeta hold promising perspective in immunotherapy. In the present work we focused on the mechanisms of anti-tumor action of effectors transduced with an anti-CD19 chimaeric receptor in the context of ...

Periapical lesions are inflammatory conditions of tooth periapical tissues, triggered by dental pulp infection and characterized by exudation of immune cells to the affected tissues and production of inflammatory mediators such as cytokines. The inflammatory periapical reaction is mainly driven by Th1, Th2, and Th17 responses, and such polarization may ...

Hepatocellular carcinoma (HCC) represents the third most common cause of cancer-related deaths worldwide and efficient treatment options are urgently needed. Based on its pathogenesis as well as a number of correlative studies, immunotherapy represents a potential therapeutic option for patients with HCC. However, tumors have also evolved numerous immune escape ...

In recent decades our understanding of immune cell activation and homeostasis has significantly expanded. Such progress helped to better define the cellular, molecular, and epigenetic networks involved in the immune response in the tumor microenvironment and renewed the enthusiasm towards the potential power of cancer immunotherapy. However, successful translation of ...

Xanthomonads are bacterial plant pathogens that cause diseases on many plant species, including important crops. Key to pathogenicity of most Xanthomonas pathovars is a Hrp-type III secretion (T3S) system that translocates effector proteins into plant cells. Within the eukaryotic cell, the effectors are thought to perform a variety of tasks ...

Chronic infection and inflammation contribute to around 25% of cancer cases worldwide. While a direct link between several types of human malignancies and inflammation has now been established, in particular at the gastrointestinal level, the relationship between inflammation and thyroid cancer and the pathophysiology of chronic inflammation that induces papillary ...

The tumor microenvironment plays a fundamental role in both the organization of and the escape from anticancer immune response. Recent experimental approaches in anticancer therapy show that some anticancer chemotherapeutics--at a different dosage than usually used--can improve tumor control by acting on immunity and can also be used in immunosuppressive ...

Wear particle-induced inflammation is a major factor contributing to aseptic loosening in peri-prosthetic tissue. The effects of cannabinoid receptor 2 (CB(2)) on wear particle-induced inflammation remain unclear. Reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to assess the effects of a CB(2)-selective antagonist, AM630, on regulation of the ...

Cellular apoptosis induced by T cells is mainly mediated by two pathways. One, granule exocytosis utilizes perforin/granzymes. The other involves signaling through death receptors of the TNF-alpha R super-family, especially FasL. Perforin plays a central role in apoptosis induced by granzymes. However, the mechanisms of perforin-mediated cytotoxicity are still not ...

BACKGROUND: Glyco-lipopeptides, a form of lipid-tailed glyco-peptide, are currently under intense investigation as B- and T-cell based vaccine immunotherapy for many cancers. However, the cellular and molecular mechanisms of glyco-lipopeptides (GLPs) immunogenicity and the position of the lipid moiety on immunogenicity and protective efficacy of GLPs remain to be determined. ...

Malignant melanoma is the deadliest form of skin cancer and is refractory to conventional chemotherapy and radiotherapy. Therefore alternative approaches to treat this disease, such as immunotherapy, are needed. Melanoma vaccine design has mainly focused on targeting CD8+ T cells. Activation of effector CD8+ T cells has been achieved in ...

Apoptosis is an early event involved in cardiomyopathy associated with diabetes mellitus. Toll-like receptor (TLR) signaling triggers cell apoptosis through multiple mechanisms. Up-regulation of TLR4 expression has been shown in diabetic mice. This study aimed to delineate the role of TLR4 in myocardial apoptosis, and to block this process through ...

Application of photothermal Optical Coherence Tomography (OCT) to detect macrophages in ex vivo rabbit arteries which have engulfed nanoclusters of gold coated iron oxide (nanorose) is reported. Nanorose engulfed by macrophages associated with atherosclerotic lesions in rabbit arteries absorb incident laser (800nm) energy and cause optical pathlength (OP) variation which ...

Delivery of DNA encoding foreign antigens into mammalian cells can induce adaptive immune responses. There are currently many DNA-based vaccines in clinical trials against infectious diseases and cancer but there is a lack of adjuvants for improvement of responses to DNA-based vaccines. Here, we show augmented systemic and mucosa-associated B ...

We previously demonstrated that direct intramuscular injection of rAAV2 or rAAV6 in wild-type dogs resulted in robust T-cell responses to viral capsid proteins, and others have shown that cellular immunity to adeno-associated virus (AAV) capsid proteins coincided with liver toxicity and elimination of transgene expression in a human trial of ...

The inability of the host immune system to control tumor growth appears to result from dominant mechanisms of immune suppression that prevent the immune system from effectively responding in a way that consistently results in tumor rejection. Among the many possible mediators of tumoral immune escape, the immunoregulatory enzyme, indoleamine ...

PURPOSE: Irradiation of cancer cells can cause immunogenic death. We used mouse models to determine whether irradiation of melanoma can enhance the host antitumour immune response and function as an effective vaccination strategy, and investigated the molecular mechanisms involved in this radiation-induced response. MATERIALS AND METHODS: For in vivo studies, ...

Neuroblastoma is one of the most common solid tumors in infancy and early childhood. Using the A/J mouse and a syngeneic neuroblastoma cell line AGN2a, we induced a strong anti-neuroblastoma cellular immune response when AGN2a transfected to express costimulatory molecules (CD80/CD86/CD54/CD137L) was used as a vaccine in the context of ...

BACKGROUND: Soluble programmed death-1 (sPD-1) has been proven to bind PD-1 ligands (PD-Ls), block PD-L/PD-1 interactions, and enhance the cytolysis of cytotoxic T-lymphocytes (CTLs). CH50, a two-domain molecule of fibronectin, has been shown to suppress the development of tumors via enhancing the activity of macrophages. This study evaluated the influence ...

In the mid-eighties of the last century, extracellular-proteolipid complexes have been identified in tumor patients and circulating RNA was suggested to represent a specific secretory product of cancer cells. The presence of specific types of RNA in a variety of cancer types proved to be useful in cancer diagnosis. It ...

The growing interest in using zebrafish for genetic and functional dissection of malignancy and infection was highlighted by the second international workshop on Zebrafish Models of Cancer and the Immune Response in Spoleto, Italy (July 20-22, 2009). The overarching theme of the state-of-the-art reports featured the unique suitability of zebrafish ...

There has been an explosion of literature focusing on the role of regulatory T (Treg) cells in cancer immunity. It is becoming increasingly clear that Treg cells play an active and significant role in the progression of cancer, and have an important role in suppressing tumor-specific immunity. Thus, there is ...

Thymoquinone (TQ) has been reported as a potent inducer of apoptosis in cancer cells. However, the role of TQ as an apoptotic or antiapoptotic has not been established yet in other types of cell injuries. Our objective was to explore whether TQ exerts a hepatoprotective effect against hepatic ischemia reperfusion ...

The aim of the study was to identify as potential therapeutic targets specific molecular alterations in tumor cells recognized by the immune system. To identify such targets, we analyzed the human leukocyte antigen (HLA) peptidomes of human melanoma cells by 2-dimensional nano-HPLC/mass spectrometry and tested the immunological significance of the ...

HPMA copolymers are one of the most promising drug carriers as their biophysical and biochemical properties, including their immunocompatibility, are very favorable. So far, there is no evidence that HPMA copolymers can interact with the immune system in a way that would lead either to suppression of some of its ...

Regulatory T (T(reg)) cells can suppress a wide variety of immune responses, including antitumor and alloimmune responses. The mechanisms by which T(reg) cells mediate their suppressive effects depend on the context of their activation. We previously reported that granzyme B is important for T(reg) cell-mediated suppression of antitumor immune responses. ...

HSP gp96-based vaccines have been trialled in rodent models and, more recently, in humans. Better understanding of gp96's immunomodulatory role will help with the design of more effective strategies for treatment of cancer and infectious diseases. In this study, we monitored the activities of T cells and activation of Treg ...

The marquee cell of the immune response, the T lymphocyte, is exquisitely sensitive to ionizing radiation. Moreover, the majority of cells of the hematopoietic lineage, with their high turnover and radiation sensitivity, are effectively ablated by relatively low radiation doses, such that total-body irradiation is an effective immunosuppressive therapy. Despite ...

Melanoma cells can play a number of tricks to evade the host immune response. They can make themselves invisible to cells of the immune system poised to attack them, elaborate molecules that are frankly immunosuppressive, and can create a microenvironment that is hostile to cells of the immune system. Efforts ...

Recent human immunodeficiency virus type 1 (HIV-1) vaccination strategies aim at targeting a broad range of cytotoxic T lymphocyte (CTL) epitopes from different HIV-1 proteins by immunization with multiple CTL epitopes simultaneously. However, this may establish an immune hierarchical response, where the immune system responds to only a small number ...

Triptolide is the principal active ingredient in extracts from the Chinese herb Tripterygium wilfordii Hook.F (TwHF), and has various functions such as immunosuppression, anti-inflammatory and antitumor properties. In diverse hematological tumors triptolide exerts antitumor activity and many studies have tried to elucidate the potential antitumor mechanism. The evidence that triptolide-induced ...