Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MHC class I and II molecules play an important role in specific interactions with cells of the immune system. Endogenous or exogenous antigens are presented to the clonotypic receptor of T cells as small peptides associated to MHC molecules. Qualitative or quantitative variation in the expression of these molecules in the surface of tumor cells could have important implications in anti-tumor immune responses. We have analysed 344 human tumors for HLA class I and II expression and found that 10-30% of tumors present a total loss of HLA ABC molecules. In addition, HLA-A or -B locus-specific losses were also detected. These alterations have been correlated with tumor aggressiveness in breast and laryngeal carcinomas. We also have observed that the expression of HLA ABC molecules in autologous metastasis did not always correspond with the expression detected in the primary tumor. In laryngeal carcinomas HLA-DR expression was associated with an excellent prognosis. We have observed in most tumors that the absence of class I molecules usually corresponds with a simultaneous loss of heavy chain and beta 2 microglobulin expression and with a low level of the mRNA specific for class I genes. Nevertheless, a variety of mechanisms are involved since in colon tumors the absence of expression is caused by beta 2 microglobulin down regulation. Also post-transcriptional mechanisms may be involved in the differential expression of HLA-A and -B locus products. There is no doubt that a more exact knowledge of the mechanisms that produce alteration in the expression of these antigens will help to manipulate MHC gene expression in human tumors and to induce a more efficient immune response.
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PMID:MHC expression on human tumors--its relevance for local tumor growth and metastasis. 191 16

Tumor-reactive T cells play an important role in cancer immunosurveillance. Applying the multimer technology, we report here an unexpected high frequency of Melan-A-specific CTLs in a melanoma patient with progressive lymph node metastases, consisting of 18 and 12.8% of total peripheral blood and tumor-infiltrating CD8+ T cells, respectively. Melan-A-specific CTLs revealed a high cytolytic activity against allogeneic Melan-A-expressing target cells but failed to kill the autologous tumor cells. Loading of the tumor cells with Melan-A peptide reversed the resistance to killing, suggesting impaired function of the MHC class I antigen processing and presentation pathway. Mutations of the coding region of the HLA-A2 binding Melan-A26-35 peptide or down-regulation of the MHC class I heavy chain, the antigenic peptide TAP, and tapasin could be excluded. However, PCR and immunohistochemical analysis revealed a deficiency of the immunoproteasomes low molecular weight protein 2 and low molecular weight protein 7 in the primary tumor cells, which affects the quantity and quality of generated T-cell epitopes and might explain the resistance to killing. This is supported by our data, demonstrating that the resistance to killing can be partially reversed by pre-exposure of the tumor cells to IFN-gamma, which is known to induce the immunoproteasomes. Overall, this is the first report of an extremely high frequency of tumor-specific CTLs that exhibit competent T-cell-effector functions but fail to lyse the autologous tumor cells. Immunotherapeutic approaches should not only focus on the induction of a robust antitumor immune response, but should also have to target tumor immune escape mechanisms.
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PMID:High frequency of functionally active Melan-a-specific T cells in a patient with progressive immunoproteasome-deficient melanoma. 1534 21

In our previous studies, we have shown that patients with serous ovarian carcinoma in advanced surgical stage disease have a particularly poor prognosis if they carry the HLA-A*02 genotype. This represent a stronger prognostic factor than loss or downregulation of the MHC class I heavy chain (HC) on tumor cells. In this study, we investigated the expression of the non-classical, immune tolerogenic HLA -G and -E on the tumor cells along with the infiltration of immune cells in the tumor microenvironment. FFPE primary tumors from 72 patients with advanced stages of serous adenocarcinoma and metastatic cells present in ascites fluid from 8 additional patients were included in this study. Both expression of HLA-G and aberrant expression of HLA-E were correlated to a significant worse prognosis in patients with HLA-A*02, but not with different HLA genotypes. Focal cell expression of HLA-G correlated to a site-specific downregulation of classical MHC class I HC products and aberrant HLA-E expression, showing a poor survival. HLA-G was more frequently expressed in metastatic cells than in primary tumor lesions and the expression of HLA-G inversely correlated with the frequency of tumor infiltrating immune cells. All these parameters can contribute together to identify and discriminate subpopulations of patients with extremely poor prognosis and can give them the opportunity to receive, and benefit of individually tailored treatments.
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PMID:Non-classical HLA-class I expression in serous ovarian carcinoma: Correlation with the HLA-genotype, tumor infiltrating immune cells and prognosis. 2694 60

Ovarian cancer is the fifth leading cause of cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. The foundation of its management consists of cytoreductive surgery (CRS) followed by systemic chemotherapy, with the completeness of surgical resection consistently identified as one of the most important prognostic factors for the disease. The goal of our investigation is the development of a near-infrared fluorescence (NIRF) imaging agent for the intraoperative imaging of high-grade serous ovarian cancer (HGSOC). As surgeons are currently limited to the visual and manual assessment of tumor tissue during CRS, this technology could facilitate more complete resections as well as serve important functions at other points in the surgical management of the disease. Elevated levels of cancer antigen 125 (CA125) have proven a useful biomarker of HGSOC, and the CA125-targeting antibody B43.13 has shown potential as a platform for immunoPET imaging in murine models of ovarian cancer. Herein, we report the development of a NIRF imaging agent based on B43.13: ssB43.13-IR800. We site-specifically modified the heavy chain glycans of B43.13 with the near-infrared dye IRDye 800CW using a chemoenzymatic approach developed in our laboratories. SDS-PAGE analysis confirmed the specificity of the conjugation reaction, and flow cytometry, immunostaining, and fluorescence microscopy verified the specific binding of ssB43.13-IR800 to CA125-expressing OVCAR3 human ovarian cancer cells. NIRF imaging studies demonstrated that ssB43.13-IR800 can be used to image CA125-expressing HGSOC tumors in subcutaneous, orthotopic, and patient-derived xenograft mouse models. Finally, ex vivo analyses confirmed that ssB43.13-IR800 can bind and identify CA125-expressing cells in primary tumor and metastatic lymph node samples from human patients with HGSOC.
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PMID:A Molecularly Targeted Intraoperative Near-Infrared Fluorescence Imaging Agent for High-Grade Serous Ovarian Cancer. 3264 4