Epstein –Barr virus strain heterogeneity impairs human T-cell immunity

AbstractThe Epstein –Barr virus (EBV) establishes lifelong infections in>  90% of the human population. Although contained as asymptomatic infection by the immune system in most individuals, EBV is associated with the pathogenesis of approximately 1.5% of all cancers in humans. Some of these EBV-associated tumors have been successfully treated by the infusion of virus-s pecific T-cell lines. Recent sequence analyses of a large number of viral isolates suggested that distinct EBV strains have evolved in different parts of the world. Here, we assessed the impact of such sequence variations on EBV-specific T-cell immunity. With the exceptions of EBNA2 and the EBNA3 fa mily of proteins, an overall low protein sequence disparity of about 1% was noted between Asian viral isolates, including the newly characterized M81 strain, and the prototypic EBV type 1 and type 2 strains. However, when T-cell epitopes including their flanking regions were compared, a substantial proportion was found to be polymorphic in different EBV strains. Importantly, CD4+ and CD8+ T-cell clones specific for viral epitopes from one strain often showed diminished recognition of the corresponding epitopes in other strains. In addition, T-cell recognition of a conserved epitope was affecte d by amino acid exchanges within the epitope flanking region. Moreover, the CD8+ T-cell response against polymorphic epitopes varied between donors and often ignored antigen variants. These results demonstrate...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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Conclusion: This review is focused not only on the mechanism by which the immune system protects us but also on the ways in which it can inflict the body and how to modulate it with therapy. Thus, understanding the interaction of a tumor with the immune system provides insights into mechanisms that can be utilized to elicit anti-tumor immune responses. Here, we have recapitulated the function of the tumor microenvironment and immune checkpoints.
Source: Current Cancer Therapy Reviews - Category: Cancer & Oncology Source Type: research
Abstract BACKGROUND: Treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with programmed cell death protein 1 (PD-1) inhibitors has been associated with risk of developing immune-mediated adverse reactions (IMARs). OBJECTIVES: This review provides nurses with an overview of the safety of PD-1 inhibitors approved by the U.S. Food and Drug Administration for recurrent or metastatic SCCHN following platinum chemotherapy, as well as recommendations for assisting with the diagnosis and management of IMARs. METHODS: PubMed® searches were conducted to iden...
Source: Clinical Journal of Oncology Nursing - Category: Nursing Authors: Tags: Clin J Oncol Nurs Source Type: research
Immunotherapy drugs have so far produced underwhelming results in prostate cancer. Now a team of researchers may have figured out why and how to make these drugs work for prostate cancer patients.
Source: Forbes.com Healthcare News - Category: Pharmaceuticals Authors: Source Type: news
AbstractGall bladder carcinoma (GBC) is a worldwide problem, with a higher incidence in areas of the world where cholelithiasis is common. As GBC is usually diagnosed in an advanced stage, the mortality is high. An understanding of the molecular pathways of carcinogenesis and the mutations involved in the development and progression of GBC could be useful in early diagnosis. Understanding molecular markers of prognosis as well as predictors of outcome could also potentially benefit patients undergoing treatment. New therapies targeting major molecular pathways and immunotherapy are exciting novel therapeutic options. This ...
Source: Indian Journal of Surgical Oncology - Category: Cancer & Oncology Source Type: research
Date: Friday, 12 06, 2019; Speaker: Greg M Delgoffe, Associate Professor, Department of Immunology , University of Pittsburgh; Building: Building 10 (Clinical Center); Lipsett Amphitheater
Source: NIH Calendar of Events - Category: American Health Source Type: events
This study identifies mechanisms mediating responses to immune checkpoint inhibitors using mouse models of triple-negative breast cancer. By creating new mammary tumor models, we find that tumor mutation burden and specific immune cells are associated with response. Further, we developed a rich resource of single-cell RNA-seq and bulk mRNA-seq data of immunotherapy-treated and non-treated tumors from sensitive and resistant murine models. Using this, we uncover that immune checkpoint therapy induces T follicular helper cell activation of B cells to facilitate the anti-tumor response in these models. We also show that B cel...
Source: Cell - Category: Cytology Source Type: research
This study aimed to improve WCTVs with xenoantigens to end immune tolerance and to further activate the adaptive immune system. In the present study, we designed a WCTV by transducing a vector encoding human FAPα (hFAPα) into murine tumour cells and evaluated its efficacy in multiple solid tumour models. Immunotherapy with this WCTV effectively delayed tumour growth and prevented recurrence. The anti-tumour responses were clearly linked to antigen-specific cytotoxic T cells, whereas CD4(+) T lymphocytes also played a role. Humoural immune responses were activated because the adoptive transfer of immunoglobulins...
Source: Artificial Cells, Nanomedicine and Biotechnology - Category: Biotechnology Tags: Artif Cells Nanomed Biotechnol Source Type: research
Response assessment in malignant lymphoma has progressively evolved in the last 20  years, leading to continuous adaptations to clinical requirements and technology improvements. The latest challenge in treatment evaluation is represented by immunomodulatory drugs, capable of stimulating response to cancer by unleashing the immune system of the host. Despite the consolidated cons ensus on the use of Deauville score and Lugano criteria for the assessment of first-line therapeutic regimens, during other lines of treatment and, particularly, during the course of immunotherapy, response parameters and clinical evidence appear less clear.
Source: PET Clinics - Category: Radiology Authors: Source Type: research
The effectiveness of cancer treatment must be assessed early in the course of the therapy so that regimens can be tailored in an individualized manner. Whole-body metabolic burden, metabolic tumor volume and total lesion glycolysis are the newer quantitative PET metrics that reflect the overall disease burden and take into account the stage of the disease, the heterogeneous intra-tumoral metabolism and uptake of PET tracer. Immunotherapy response evaluation in solid tumors is challenging, and combined use of anatomical and molecular imaging could evolve as the optimal way for assessing treatment response to immunotherapy. ...
Source: PET Clinics - Category: Radiology Authors: Source Type: research
Authors: von Dücker L, Hüning S, Kähler K, Terheyden P, Nashan DRT Abstract In the context of supportive therapy, possible complaints which may be caused by the cancer itself, by the antitumoral therapy or by psychosocial concerns are considered. Due to the introduction of new anticancer drugs in dermato-oncology, clinicians are confronted with a novel spectrum of adverse events. There are a number of inflammatory, immune-mediated side effects caused by immunotherapies, which can affect virtually any organ. Targeted therapies also have specific side effects. Basically, the management of adv...
Source: Der Hautarzt: Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete - Category: Dermatology Tags: Hautarzt Source Type: research
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