246 research outputs found
The Immunophenotyping of primary diffuse large B-cell lymphomas of the central nervous system
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Vaccine therapy in NHL: future promises and current limitations
No full textRecent advances in genomics are revealing new molecular targets for vaccination strategies in cancer, and unraveling the immune pathways that must be activated. Initially, work focused on idiotypic antigen expressed by the clonal immunoglobulin (Ig) of B-cell tumors. This involved assembling the encoding VH and VL genes as single-chain Fv (scFv), which has been fused to Fragment C (FrC) of tetanus toxin to enhance recognition and response. The fusion gene induces strong anti-idiotypic protection against lymphoma in experimental models, and is now in clinical trials with encouraging results emerging. This principle of fusing a pathogen-derived sequence is widely applicable. A coat protein from a potato virus substituted for the FrC sequence has also been found to be capable of promoting anti-tumor immunity. The current design is effective in inducing anti-idiotypic (Id) antibody and CD4+ T-cell attack. For intracellular tumor antigens expressed as MHC Class I-associated peptides, a design consisting of a gene encoding a single domain of FrC linked to a candidate peptide sequence has been developed. This induces fast cytotoxic T-cell attack on peptide-expressing tumor cells. Injection of DNA appears safe and clinical trials will test the efficacy of this approach, and probably lead to improvements in these flexible vaccines
Serum is not required for ex vivo IFN-gamma ELISPOT: a collaborative study of different protocols from the European CIMT immunoguiding program
No full textThe Cancer Immunotherapy Immunoguiding Program has conducted an IFN-gamma ELISPOT proficiency panel to examine the influence of serum supplementation of test media on assay performance. Sixteen European laboratories analyzed the same PBMC samples using different locally established protocols. Participants generated two simultaneous data sets-one using medium supplemented with serum and one without serum. Performances of the two test conditions were compared by quantifying: (1) the number of viable cells, (2) background spot formation induced in the medium only control and (3) the ability to detect antigen-specific T cell responses. The study demonstrated that the number of viable cells recovered and the overall background spot production were not significantly different between the two conditions. Furthermore, overall laboratory performance was equivalent for the two test conditions; 11 out of 16 laboratories reported equal or greater detection rates using serum-free medium, while 5 laboratories reported decreased detections rates under serum-free conditions. These results show that good performance of the IFN-gamma ELISPOT assay can be achieved under serum-free conditions. Optimization of the protocol for serum-free conditions should result in excellent detection rates and eliminate the requirement of serum batch and stability testing, allowing further harmonization of the assay
The adaptive immune response to colorectal cancer: from the laboratory to clinical practice
No full textAn increasing body of evidence supports that visibility of colorectal cancer to immune attack is substantial and that it limits disease progression. Analysis of the adaptive immune infiltrate in resected colorectal cancer specimens offers prognostic information which is independent of conventionally measured parameters and potentially superior in predictive value
First case report of Muir-Torre syndrome associated with non-small cell lung cancer
No full textThe eponymous Muir–Torre syndrome (MTS) is a clinical variant of hereditary non polyposis colorectal cancer, and is defined as an autosomal dominant condition with simultaneous sebaceous neoplasms of the skin and visceral malignant disease resulting from germline mutations in the DNA mismatch repair (MMR) genes. To date the most common visceral malignancy described is colorectal cancer, which is seen in approximately 50% of cases. Other clearly associated tumours include endometrial adenocarcinomas, urothelial transitional cell carcinomas, upper gastrointestinal adenocarcinomas, sebaceous adenomas and ovarian (often mucinous) carcinomas. Here we report the first recorded case of adenocarcinoma of the lung with loss of MMR gene function to be identified in a patient with MTS. The MMR deficient lung tumour demonstrated less aggressive clinical behaviour compared with a synchronous MMR proficient lung adenocarcinoma
Patient selection for anti-PD-1/PD-L1 therapy in advanced non-small-cell lung cancer: implications for clinical practice
No full textImmune checkpoint inhibitors (ICIs) targeting PD-1 or PD-L1 represent a standard treatment option for patients with advanced non-small-cell lung cancer. However, a substantial proportion of patients will not benefit from these treatments, and robust biomarkers are required to help clinicians select patients who are most likely to benefit. Here, we discuss the available evidence on the utility of clinical characteristics in the selection of patients with advanced non-small-cell lung cancer as potential candidates for single-agent anti-PD-1/PD-L1 therapy, and provide practical guidance to clinicians on identifying those patients who are most likely to benefit. Recommendations on the use of immune checkpoint inhibitor in clinically challenging populations are also provided
DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire
No full textThe majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4+ T cell help. Candidate MHC class Ibinding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitopederived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag-transgenic (gag-Tg) mice. Vaccination with the construct induced epitopespecificIFN-c-producing CD8+ T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8+ T cell responses from a residual tolerized repertoire
Universal N-glycosylation sites introduced into the B-cell receptor of follicular lymphoma by somatic mutation: a second tumorigenic event?
No full textGenes in FL commonly acquire sequence motifs by somatic mutation that serve as sites for N-glycosylation.1 We further showed that subsets of aggressive B NHL acquire sites2
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