An estimated 15% or more of the cancer burden worldwide is attributable to known infectious agents. We screened colorectal carcinoma and matched normal tissue specimens using RNA-seq followed by host sequence subtraction and found marked over-representation of Fusobacterium nucleatum sequences in tumors relative to control specimens. F. nucleatum is an ...

Our previous report indicated that carbon ion beam irradiation upregulated membrane-associated immunogenic molecules, underlining the potential clinical application of radioimmunotherapy. The antimetastatic efficacy of local combination therapy of carbon ion radiotherapy and immunotherapy was examined by use of an in vivo murine model. Tumors of mouse squamous cell carcinoma (NR-S1) ...

Abstract Despite the advantages of using adenoviral vectors for specific antigenic gene delivery in the development of antigen-presenting cell (APC)-based vaccines, the lack of the coxsackievirus-adenovirus receptor (CAR) on APCs limits the use of adenoviral vectors for in vitro gene delivery. In this study, we used a recombinant adapter protein, ...

Tumor-associated dendritic cells (DCs) often induce T cell anergy or deletion and regulatory T cells instead of antitumor immunity. Although many tumor-associated Ags have been found, there is still no effective vaccine for cancer. Thus, novel rational strategies to enhance the immunogenicity of cancer-specific Ags are needed. Chromosome 1 open ...

Little preclinical modeling currently exists to support the use of OX40 agonists as therapeutic agents in the setting of advanced cancers, as well as the mechanisms through which therapeutic efficacy is achieved. We show that treatment of mice bearing well-established day 17 sarcomas with a novel OX40 ligand-Fc fusion protein ...

We investigated possible cellular receptors for the human CXC chemokine platelet factor-4 variant/CXCL4L1, a potent inhibitor of angiogenesis. We found that CXCL4L1 has lower affinity for heparin and chondroitin sulfate-E than platelet factor-4 (CXCL4) and showed that CXCL10 and CXCL4L1 could displace each other on microvascular endothelial cells. Labeled CXCL4L1 ...

Tumor-associated immunosuppressive strategies, such as lack of tumor antigen recognition and failure of lymphocyte activation and homing, resist the development of tumor-specific immunity and hamper the immune response-mediated elimination of cancerous cells. In this report, we show that reovirus virotherapy overrides such a tumor immune evasion and establishes clinically meaningful ...

J Oral Pathol Med (2011) 40: 263-269 Background:  The purpose of this study was to assess and compare angiogenesis with proliferative activity in Keratocystic odontogenic tumors (KCOT) and dentigerous cysts (DC) by using monoclonal mouse anti-human antibody against CD105 (endoglin). Material and Methods:  Angiogenesis was assessed in 38 KCOT, 27 ...

Tumor microenvironment has emerged as one of the major obstacles against the clinical efficacy of dendritic cell (DC) vaccines. Tumor-derived IL-6 may inhibit the differentiation of hematopoietic progenitor cells into DCs and suppress DC maturation, rendering DCs tolerogenic. We hypothesized that silencing the IL-6 receptor alpha chain (IL-6Rα) would restore ...

The question as to whether the tumor grows because of or despite the host immune system is being progressively addressed with refined technology, gene targeting in mice and human translational research. The productive interplay between major actors of the antitumor immunity is actively compromised by the tumor microenvironment subverting the ...

Our previous studies have revealed that nicotine-treated immature dendritic cells (imDCs) have anti-tumor effects in murine lymphoma models. The present study is to explore the preventive and therapeutic anti-tumor effects of nicotine-treated imDCs in murine lung and liver cancer. To address this objection, bone marrow-derived imDCs were firstly stimulated by ...

It has been reported that the heparanase epitope can elicit a CTL-mediated anti-tumor response; however, the potential of the heparanase epitope modified by an endoplasmic reticulum (ER) retrieval signal, a C-terminal Lys-Asp-Glu-Leu sequence, is still unknown. The heparanase epitope was modified by ER retrieval signal, and dendritic cells (DC) were ...

Antigen-specific T cells can be induced by direct priming and cross-priming. To investigate cross-priming as a vaccination approach dendritic cells were transfected with cytopathogenic viral RNA-replicons that expressed domains of the tumor-associated Her2-antigen and injected into MHC-discordant mice that did not allow direct priming. Upon tumor challenge 75% of the ...

The beneficial properties of β-glucans have been recognized for centuries. Their proposed mechanisms of action in cancer therapy occur via stimulation of macrophages and priming of innate neutrophil complement receptor 3 for eliciting complement receptor 3-dependent cellular cytotoxicity of iC3b-opsonized tumor cells. The current study is to investigate whether β-glucan ...

Recent evidence suggested that angiogenesis played a pivotal role in the development of hepatocellular carcinoma cells (HCC), thus the therapy strategy targeting antiangiogenesis has been regarded as promising method for HCC therapy. Tumor endothelial marker 8 (TEM8) is a recently described protein that is preferentially expressed within tumor endothelium. However, ...

Dendritic cell (DC)-based immunotherapy can trigger effective immune responses against cancer in human patients. Although accompanied by little toxicity, further improvements are needed to optimize immune responses for fully satisfactory clinical outcomes. IFNγ, a potent inducer of T helper type 1 immune responses, is considered an important tool to realize ...

Tumor-associated antigens (TAAs) are known to be immunotherapy targets; thus tumor-sharing TAA may be used as a fusion hybrid partner to confer protection against subsequent tumor challenge. The squamous cell carcinomas (SCCs), SCCVII and B4B8, were used in C3H/HEN mice: SCCVII (H-2(k)) is syngeneic, B4B8 (H-2(d)) is allogeneic. Experiments using ...

Immunologic approaches to combat cancer aim at the induction of tumor-reactive immune responses to achieve long-term protection. In this context, we recently developed a transcutaneous immunization (TCI) method using the Toll-like receptor (TLR) 7 agonist imiquimod and a peptide epitope. Application onto intact skin induces potent cytotoxic T lymphocyte (CTL) ...

Tumor cell vaccination with irradiated autologous tumor cells is a promising approach to activate tumor-specific T cell responses without the need for tumor Ag identification. However, uptake of dying cells by dendritic cells (DCs) is generally a noninflammatory or tolerizing event to prevent the development of autoreactive immune responses. In ...

Antigen-presenting dendritic cells (DCs) trigger the activation of cytotoxic CD8 T cells that target and eliminate cells with the antigen on their surface. Although DCs usually pick up and process antigens themselves, they can also receive peptide antigens from other cells via gap junctions. We demonstrate here that infection with ...

Encapsulation of tumor-associated antigens in polymer nanoparticles (NP) is a promising approach to enhance efficiency of antigen delivery for anti-tumor vaccines. Head and neck squamous carcinoma (HNSCC) cell lines were initially used to generate tumor-associated antigens (TAA)-containing poly (lactic-co-glycolic acid) (PLGA) NP; encapsulation efficiency and release kinetics were profiled. Findings ...

BACKGROUND: Carbon-ion beam (CIB) treatment is a powerful tool for controlling primary tumors in the clinical setting. However, to date, few clinical or experimental studies have investigated the effects of CIB treatment on tumor recurrence and antitumor immunity. METHODS: A multiple challenge test was performed using syngenic and nude mouse ...

Targeting CD40, a member of the tumor necrosis factor superfamily, using agonist antibodies (Abs) produces dramatic antitumor effects. Indeed, high-dose intravenous anti-CD40 Ab 'licenses' dendritic cells (DCs) that instruct activated CD8(+) cytotoxic T cells to leave lymph nodes (LNs) and penetrate the mesothelioma tumor microenvironment. However, toxic side effects and ...

BACKGROUND: Several types of viral-transduced HER2/neu-modified dendritic cells (DC(HER2/neu)) have been used for preventing and/or treating HER2/neu-overexpressing tumors. However, to date, lentivirus has not been used to generate HER2/neu-modified DCs. METHODS: In the present study, we used recombinant lentivirus containing a truncated neu gene (rLVneu) to transduce murine bone marrow-derived ...

Efficient tumor vaccination frequently requires adjuvant. Concomitant induction of an autoimmune response is discussed as a means to strengthen a weak tumor Ag-specific response. We asked whether the efficacy of dendritic cell (DC) vaccination with the renal cell carcinoma Ags MAGE-A9 (MAGE9) and G250 could be strengthened by covaccination with ...

Introduction: Langerhans/dendridic cell sarcomas (L/DCS) are rare neoplasms that have rarely been reported to originate from malignant lymphomas. Tumor course can vary from spontaneous regression to aggressive disease. Biphasic progression of hairy cell leukemia to L/DCS has not been previously reported. We describe a case of L/DCS resulting from HCL. ...

BACKGROUND: The aim of the present study was to evaluate the therapeutic efficacy of dendritic cell (DC)-tumor fusion hybrids with Toll-like receptor (TLR) agonists. METHODS: DC-tumor fusion hybrids were generated by electrofusion and injected into the inguinal lymph nodes of C57BL/6 mice with 3-day established pulmonary metastases. Paired TLR agonists ...

One of the clear paradoxes in tumor immunology is the fact that cross-presentation of cell-associated tumor antigens to CD8(+) T cells is efficient, yet CTL generation is weak, and tumors continue to grow. We examined, for the first time whether this may be due to alterations in the phenotype or ...

This study examined whether 1-methyl-tryptophan [1-MT, an indoleamine 2, 3-dioxygenase (IDO) inhibitor] could reduce CD4+CD25+ regulatory T cells (Tregs) proliferation and improve the anti-tumor efficacy of dendritic cells (DCs) pulsed with tumor cell lysate in the mice bearing pancreatic adenocarcinoma. The models of pancreatic adenocarcinoma were established in C57BL/6 mice ...

Dendritic cells (DCs) play a critical role in generating anti-tumor immunity. DC functional defect has been related to the growth and progression of various human cancers. In esophageal squamous cell carcinoma (ESCC), the examination of DCs using immunohistochemistry (IHC) with anti-S100 antibody has demonstrated an increased infiltration of DCs into ...

Topoisomerase II alpha (Top2alpha) is an attractive candidate to be used as a tumor antigen for cancer immunotherapy, because it is abundantly expressed in various tumors and serves as a target for a number of chemotherapeutic agents. In this study, we demonstrated the immunogenicity of Top2alpha, using dendritic cells (DC) ...

Transcatheter arterial embolization (TAE) destroys a tumor by the induction of necrosis and/or apoptosis and causes inflammation with cytokine production, which may favor immune activation and presentation of tumor-specific antigens. In the current study, we attempted to identify the effect of TAE on tumor-specific T-cell responses and the additional effect ...

The tumor environment exerts a powerful suppressive influence on infiltrating tumor-reactive T cells. It induces tolerance of adoptively transferred effector T cells as they enter tumors and maintains the tolerance of persisting tumor-infiltrating T cells. In an autochthonous prostate cancer model, in which tumor-reactive CD8 T cells are trackable, we ...

Transfer of tumor antigen-specific T-cell receptors (TCRs) into human T cells aims at redirecting their cytotoxicity toward tumors. Efficacy and safety may be affected by pairing of natural and introduced TCRalpha/beta chains potentially leading to autoimmunity. We hypothesized that a novel single-chain (sc)TCR framework relying on the coexpression of the ...

The immunohistochemical analysis was used to evaluate the expression of PD-L1 in 109 non-small cell lung cancer (NSCLC) tissues and para-tumor tissues. Associations between expressed PD-L1 and tumor histological types, degree of differentiation, and lymph node metastasis were calculated, and overall survival was assessed. Meanwhile, immunohistochemistry and immunofluorescence double labeling ...

Constitutively activated signal transducer and activator of transcription-3 (STAT3) in tumor and dendritic cells (DCs) plays a critical role in tumor-induced immunosuppression. This is considered a major challenge in effective immunotherapy of cancer. Herein we describe the development of a polymeric nanocarrier for the delivery of JSI-124 (a small molecule ...

Plasmacytoid dendritic cell (PDC) is a Th2-type dendritic cell precursor. It is an important professional effector cell characterized by its capacities to produce large amount of alpha interferon and to differentiate into dendritic cell. PDCs are scarce in normal condition. They circulate in the blood as veiled cells and enter ...

A dendritic cell vaccine has been developed as a novel strategy for generating antitumor immunity in the treatment of cancer. The purpose of this study was to assess the maximal tolerated dose, safety, and immunologic response of a new dendritic cell vaccine (DC-Vac) into which tumor lysate was loaded by ...

Two major distinct subsets of dendritic cells (DCs) are arranged to regulate our immune responses in vivo; 33D1(+) and DEC-205(+) DCs. Using anti-33D1-specific monoclonal antibody, 33D1(+) DCs were successfully depleted from C57BL/6 mice. When 33D1(+) DC-depleted mice were stimulated with LPS, serum IL-12, but not IL-10 secretion that may be ...

Tolerogenic dendritic cells in the tumor microenvironment can inhibit the generation and maintenance of robust antitumor T cell responses. In this study, we investigated the effects of local delivery of CD40L by tumor-reactive CD8(+) T cells on dendritic cell activation and antitumor T cell responses in the TRAMP model. To ...

We previously found that dendritic cell (DC) precursors could be recruited into the peripheral blood of B6 mice by administration of macrophage inflammatory protein (MIP)-1alpha. These MIP-1alpha-recruited DCs could induce anti-tumor protective immunity when pulsed with tumor cell lysate. In this study, MIP-1alpha-recruited DCs could not effectively suppress preestablished tumor ...

Tumor-mediated immune suppression occurs through multiple mechanisms, including dysregulation of dendritic cell differentiation. This block in differentiation results in fewer dendritic cells and an accumulation of immunosuppressive myeloid- derived suppressor cells and is thought to contribute to tumor outgrowth and to act as an impediment to successful anti-cancer immunotherapy. Tumor-mediated ...

Junctional adhesion molecule-A (JAM-A)-null dendritic cells (DCs) are more motile and effective than their wild-type counterpart in promoting contact hypersensitivity reaction. Here, we show that the growth and aggressiveness of pancreatic islet cell carcinoma induced by SV40 T antigen expression in beta cells (Rip1Tag2 mice) are significantly reduced in JAM-A-null ...

Regulatory T (Treg) cells limit the onset of effective antitumor immunity, through yet-ill-defined mechanisms. We showed the rejection of established ovalbumin (OVA)-expressing MCA101 tumors required both the adoptive transfer of OVA-specific CD8(+) T cell receptor transgenic T cells (OTI) and the neutralization of Foxp3(+) T cells. In tumor-draining lymph nodes, ...

Adoptive immunotherapy with tumor-specific T cells represents a promising treatment strategy for patients with malignancy. However, the efficacy of T-cell therapy has been limited by the ability to expand tumor-reactive cells with an activated phenotype that effectively target malignant cells. We have developed an anticancer vaccine in which patient-derived tumor ...

Dendritic cell (DC)-based tumor vaccine is an attractive modality for the treatment of hormone-refractory prostate cancer (HRPC) because it has some efficacy and few side effects in patients with poor general conditions. The aim of this study was to establish which is the most effective DC vaccine for the treatment ...

Dendritic cells (DCs), essential for the initiation and regulation of adaptive immune responses, have been used as anticancer vaccines. DCs may also directly trigger tumor cell death. In the current study, we have investigated the tumoricidal and immunostimulatory activities of mouse bone marrow-derived DCs. Our results indicate that these cells ...

This article provides a broad overview of the data, including laboratory and clinical studies, currently available on the combination of immunotherapy and chemotherapy for treating cancer. The various forms of immunotherapy combined with chemotherapy include monoclonal antibodies, adoptive lymphocyte transfer, or active specific immunotherapy, such as tumor proteins, irradiated tumor ...

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that are critical for the generation of effective cytotoxic T lymphocyte (CTL) responses; however, their function and phenotype are often defective or altered in tumor-bearing hosts, which may limit their capacity to mount an effective tumor-specific CTL response. In particular, the manner ...

Since decades, the main goal of tumor immunologists has been to increase the capacity of the immune system to mediate tumor regression. Considerable progress has been made in enhancing the efficacy of therapeutic anticancer vaccines. First, dendritic cells (DCs) have been identified as the key players in orchestrating primary immune ...