Search results for " present"

Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma.

2001

In cervical carcinomas abnormalities in the MHC class I surface expression are a frequent event, which are often associated with the deficient expression of the peptide transporter subunit TAP1 thereby resulting in impaired T cell response. In order to understand the role of other components of the MHC class I antigen processing machinery (APM) in the immune escape, 16 surgically removed primary cervical carcinoma lesions were analyzed for their mRNA expression of the heterodimeric peptide transporter TAP, the constitutive and interferon (IFN)-gamma inducible proteasome subunits and their activators PA28alpha/beta, various chaperones as well as MHC class I antigens. High expression levels o…

HLA class I antigen abnormalities and immune escape by malignant cells

2002

Abbreviations used in this paper: APM, antigen processing machinery; β2m,β2 microglobulin; bp, base pair; CTL, cytotoxic T lymphocytes; ER, endoplasmic reticulum; HC, heavy chain; HNSCC, head and neck squamous cell carcinoma; IFN, interferon; IL, interleukin; KIR, killing inhibitory receptors; LMP, low molecular weight proteins; LOH, loss of heterozygosity; mAb, monoclonal antibody; MHC, major histocompatibility complex; NK, natural killer; PA, proteasome activator; PCR, polymerase chain reaction; RCC, renal cell carcinoma; SCLC, small cell-lung carcinoma; TAA, tumor-associated antigens; TAP, transporter associated with antigen processing; TCR, T cell receptor; TNF, tumor necrosis factor; w…

In the literature: June 2020.

2020

Immunotherapy based on checkpoint blockade has revolutionised cancer treatment during last years. Whereas this approach fails in a relevant group of patients, the knowledge on tumour microenvironment (TME) opened the possibility to the use of additional therapeutic strategies to potentiate antitumour immunity, including depletion of protumourigenic or immune suppressive and activation of specific immune populations using agonistic antibodies. Nevertheless, due to the complexity of the TME, many of these strategies have been indiscriminately advanced to the clinic without clear mechanistic hypotheses. Nowadays, single-cell RNA sequencing (scRNA-seq)-based transcriptome analyses identify T ce…

P11.09 Pan-RTK inhibition of sLRIG1 mediates AXL downregulation in Glioblastoma

2019

Abstract INTRODUCTION Aberrant regulation of receptor tyrosine kinase (RTK) activity is characteristic of Glioblastoma (GBM). However, RTK-based targeted therapies have been largely unsuccessful in GBM patients, partially due to the complexity and redundance of RTK signaling. LRIG1 (Leucine-rich Repeats and ImmunoGlobulindomains protein 1) is known as an endogenous inhibitor of epidermal growth factor receptor (EGFR) during health and disease, however its mechanism of action is poorly understood. We previously showed that the soluble form of LRIG1 potently inhibits of GBM growth in vivo, irrespective of EGFR expression level and status, suggesting the involvement of other RTKs. Here, we aim…

Impaired HLA-class-I stability in a sarcoma cell line which stimulates exclusively HLA-class-II-restricted autologous T cells

1996

Defects in the generation and transport of antigenic peptides within tumor cells will lead to the expression of unstable HLA-class-I molecules on the cell surface. These defects will allow tumor cells to escape an MHC-class-I-restricted T-cell response. Recently, we described an exclusively HLA-class-II-restricted autologous T-cell response against a human sarcoma cell line MZ-MES-1 in vitro. Here, we show that surface HLA-class-I molecules of MZ-MES-1 cells are unstable at physiological temperature. HLA-class-I surface expression of MZ-MES-1 cells could be strongly enhanced by culture at low temperature in contrast to various other cell lines analyzed in parallel. Furthermore, culture at l…

Naturally processed and HLA-B8-presented HPV16 E7 epitope recognized by T cells from patients with cervical cancer.

2004

Several major histocompatibility complex (MHC) alleles have been reported to present peptides derived from the HPV16 E7 oncoprotein to T cells. We describe an overrepresentation of the HLA-B8 allele (28.44%) in cervical cancer patients as compared to the MHC class I allele frequency in a local healthy control population (18.80%) and the identification of an HLA-B8-binding peptide TLHEYMLDL (HPV16 E77–15), which is able to drive HPV16 E7-specific and MHC class I-restricted T-cell responses in peripheral blood lymphocytes from healthy individuals. TLHEYMLDLspecific T cells recognize the naturally processed and presented peptide on HPV16 cervical cancer cells transfected with the HLA-B8 gene d…

Regulation of CD1d expression by murine tumor cells: escape from immunosurveillance or alternate target molecules?

2002

alpha beta+ TCR T cells recognize peptide fragments displayed by MHC-class I or -class II molecules. Recently, additional mechanisms of antigen recognition by T cells have been identified, including CD1-mediated presentation of nonpeptide antigens. Only a limited number of CD1 antigens is retained in the mouse, i.e., the group II CD1 antigens, which are split into CD1D1 and CD1d2. Several T cell subsets have been shown to interact with murine CD1 antigens, including NK cells or "natural T cells" with the invariant V alpha 14 J alpha 281 TCR chain. Even if TAP defects may prevent classical endogenous antigen presentation in tumor cell lines, antigen presentation via CD1 is still functional. …

Partial tyrosinase-specific self tolerance by HLA-A*0201-restricted cytotoxic T lymphocytes in mice and man

2003

The human tyrosinase (hTyr) (369-377) cytotoxic T lymphocyte (CTL) epitope is presented by malignant melanoma and various nontransformed cells in association with human leukocyte antigen (HLA)-A*0201 (A2.1) and used for vaccination-based immunotherapy of melanoma patients. Its mouse homologue, mTyr (369-377), is naturally processed and bound by A2.1 with equivalent efficacy and thus enabled us to explore the effect of self tolerance on Tyr-specific T cells in different lines of A2.1 transgenic (Tg) mice and man. We found that self Tyr-reactive CTL in Tg mice and, importantly, in man were affected by partial tolerance resulting in only residual T lymphocytes of higher avidity for self Tyr al…

OS1.5 Harnessing soluble LRIG1 for pan-RTK targeting in glioblastoma

2018

INTRODUCTION: The role of receptor tyrosine kinases (RTKs) in glioblastoma is widely acknowledged. However, therapies based on RTK targeting have been continuously unsuccessful in GBM patients, highlighting the complexity of RTK signaling and biology. LRIG1 (Leucine-rich Repeats and ImmunoGlobulin domains protein 1) was identified as an endogenous inhibitor of epidermal growth factor receptor (EGFR) and other RTKs, and was confirmed as a tumor suppressor in various cancer types. We previously identified the soluble form of LRIG1 as a potent inhibitor of GBM growth in vivo, irrespective of EGFR status. Here, we aim to shed light on the molecular mechanisms underlying its anti-cancer activity…

2004

Address: 1I. Medical Department, University of Mainz, Langenbeckstr.1, D-55101 Mainz, Germany, 2Deutsches Krebsforschungszentrum, Applied Tumor Virology, Dept. F0100, and Institut National de la Sante et de la Recherche Medicale Unite 375, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany, 3III. Medical Department, University of Mainz, Langenbeckstr.1, D-55101 Mainz, Germany and 4Med. Department Mitte, Klinikum Dortmund GmbH, Beurhausstr. 10, 44137 Dortmund, Germany