A novel epitope of N-CAM defines precursors of human adherent NK cells

AbstractActivated, adherent natural killer (A-NK) cells represent a distinct subpopulation of interleukin (IL)-2-stimulated NK cells, which are selectively endowed with the increased expression of integrins and ability to adhere to solid surfaces, migrate into, infiltrate, and destroy cancerous tissues. The present study defines the phenotype and functions of precursors of A-NK (pre-A-NK) cells in humans. Peripheral blood pre-A-NK cells, in contrast to the rest of NK cells, express a novel epitope of CD56 neuronal cell adhesion molecule, termed ANK-1, and increased cell-surface levels of integrins. Pre-A-NK cells also express low levels of CD56 and CD161, and some express CD162 receptor, do…

Antigen recognition by T cells: a strong sense of structure

Radiation response non-invasively imaged by [18F]FDG-PET predicts local tumor control and survival in advanced oral squamous cell carcinoma

It is a major challenge to preoperatively identify patients who will profit from surgery of advanced oral cancer. In multimodality therapy, response to neoadjuvant radiation correlates to treatment success. Hence, for preoperative decisions, assessment of treatment response is required. Therefore, we analysed the prognostic significance of glucose metabolism after preoperative radiotherapy. [(18)F]FDG-PET investigations were performed for re-staging 35 patients after neoadjuvant radiotherapy (36Gy) immediately prior to tumor resection. Emission and transmission measurements were obtained and SUV's were calculated for the sites of maximum [(18)F]FDG-uptake. Subpopulations of "low" (SUV4) and…

Histotomography of the odontoblast processes at the dentine-enamel junction of permanent healthy human teeth in the confocal laser scanning microscope

The translucency of teeth allows the non-destructive subsurface visualisation of their microstructure by confocal laser scanning microscopy (CLSM) at a level of about 150 μm below the surface. The dentine–enamel junction (DEJ) is accessible only directly adjacent to the cervix of the tooth. Therefore teeth have to be sectioned for studying marginal areas of the dental hard tissue. The potential of the technique for (pseudo) three-dimensional visualisation allows the study of an array of individual confocal images, the interpretation of which is similar to that of macroscopic tomographs (CT-scan, MRI). Additionally, the extended focus mode yields the overlay of individual confocal images in …

Diagnostik des oralen Plattenepithelkarzinoms und seiner Präkursorläsionen

The number of intratumoral dendritic cells and ?-chain expression in T cells as prognostic and survival biomarkers in patients with oral carcinoma

BACKGROUND Dendritic cells (DCs) are antigen-presenting cells with a unique ability to cross prime T cells and generate strong antitumor responses. This study evaluates the presence and prognostic significance of DCs as well as functional T cells, which accumulate in the microenvironment in patients with oral squamous cell carcinoma (OSCC). METHODS Immunohistochemistry for S-100 positive or p55 positive DCs and for T-cell receptor (TcR)-associated ζ-chain expression in tumor-infiltrating lymphocytes (TILs) was performed in 132 paraffin embedded specimens from patients with primary OSCC. The median clinical follow-up for the patients was 50 months. The numbers of intratumoral DCs or TILs exp…

Defects in the Human Leukocyte Antigen Class I Antigen Processing Machinery in Head and Neck Squamous Cell Carcinoma: Association with Clinical Outcome

AbstractPurpose: Human leukocyte antigen (HLA) class I antigen defects, which are frequently present in head and neck squamous cell carcinoma (HNSCC) cells may provide the tumor with an escape mechanism from immune surveillance. Scanty information is available about mechanisms underlying HLA class I antigen defects in both lesions and cell lines from HNSCC. In this study, we investigate the role of antigen processing machinery (APM) component abnormalities in the generation of deficient HLA class I surface expression of HNSCC cells.Experimental Design: Using immunohistochemistry, Western blot, and RT-PCR analyses we correlated the expression of the IFN-γ inducible proteasome subunits and of…

Monoclonal TCR mRNA transcripts are preferentially detected in the TCR variable alpha chain in CD8(+) T-lymphocytes: implications for immunomonitoring.

Clinical trials have started to implement tumor-associated antigens in the form of antigenic peptides in order to augment CD8(+) T-cell responses directed against autologous cancer cells. One of the surrogate markers for successful immunization is the characterization of T-lymphocytes reacting to the immunizing peptide as determined by CDR3-length and DNA-sequence analysis. Most of the recent studies examining ex vivo T-cell responses in patients with cancer have focussed on expression and prevalence of the TCR Beta variable region, predominantly in non-sorted T-cell populations. Here, we show that clonal T-cell receptors (TCRs), as defined by DNA-fragment analysis and DNA-sequencing, appea…

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

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. …

Diagnosis of oral squamous cell carcinoma and its precursor lesions

Improvement of survival rate and quality of life after treatment of oral squamous cell carcinoma as well as cost reduction requires reliable early diagnosis of the tumor and its precursor lesions. Four different screening methods are primarily employed: toluidine blue staining (visually detected lesions: sensitivity 70-100%, specificity 25-67%), photodynamic diagnosis (sensitivity 94-99%, specificity 60-89%), autofluorescence (no data published so far) and modern oral cytology (sensitivity 80%,specificity 95-100%). Additional analytic procedures such automated image analysis, DNA image cytometry and immunocytochemistry can be used to enhance the low sensitivity of conventional oral cytology…

H2-M, a facilitator of MHC class II peptide loading, and its negative modulator H2-O are differentially expressed in response to proinflammatory cytokines

H2-M is a major histocompatibility complex (MHC) class II-like molecule that catalyzes peptide binding to MHC class II molecules. Recently, the H2-O heterodimer, encoded by H2-Oa and H2-Ob in the MHC class II region, has been shown to be physically associated with H2-M in B cells and to downregulate H2-M function. Examination of H2-O expression in freshly isolated mouse organs revealed that H2-Oa- and H2-Ob-specific transcripts are present in both lymphoid and nonlymphoid tissues. To evaluate the gene regulation and functional impact of H2-O on antigen presentation, we examined the effects on MHCII, invariant chain (Ii), H2-M, and H2-O gene expression of interleukin (IL)-4, IL-10, and inter…

A Double-Blind Randomized Controlled Trial (RCT) of Titanium-13Zirconium versus Titanium Grade IV Small-Diameter Bone Level Implants in Edentulous Mandibles - Results from a 1-Year Observation Period

Background: The use of endosseous dental implants has become common practice for the rehabilitation of edentulous patients, and a two-implant overdenture has been recommended as the standard of care. The use of small-diameter implants may extend treatment options and reduce the necessity for bone augmentation. However, the mechanical strength of titanium is limited, so titanium alloys with greater tensile and fatigue strength may be preferable. Purpose: This randomized, controlled, double-blind, multicenter study investigated in a split-mouth model whether small-diameter implants made from Titanium-13Zirconium alloy (TiZr, Roxolid™) perform at least as well as Titanium Grade IV implants. Me…

Immunotherapy with effector cells and IL-2 of lymph node metastases of human squamous-cell carcinoma of the head and neck established in nude mice

We have previously reported that immune anti-tumor effector cells, both cytotoxic T lymphocytes (CTLs) and IL-2-activated natural killer (A-NK) cells, are effective at eliminating human head-and-neck cancer (HNC) targets in vitro and in vivo in xenograft models. In this study, these 2 types of human effector cell were compared for the ability to prevent the development of lymph node metastases in a metastasis model of human squamous-cell carcinoma of the head and neck (SCCHN) established in nude mice. A tumor cell line, OSC-19, was injected into the floor of the mouth in nude mice, and the tumor grew progressively and metastasized to cervical lymph nodes by day 21. As effector cells, a huma…

Das basaloide Plattenepithelkarzinom (BSC) der Mundschleimhaut

The basaloid-squamous carcinoma (BSC) that was first described in 1986 by Wain et al. for the head and neck region is a rare distinct variant of squamous cell carcinoma (SCC). The cardinal histopathologic feature is a biphasic cellular pattern of basaloid and squamous components. BSC has been confused with solid adenoid cystic carcinoma (ACC). Although the number of reported cases is small, BSC appears biologically virulent, with a propensity to aggressive local behavior, early regional and distant metastasis, and subsequent poor survival. We report the clinicopathological characteristics of 4 new cases and compare their immunohistochemical features with those of solid ACC and conventional …

H2-Mβ1 and H2-Mβ2 Heterodimers Equally Promote CLIP Removal in I-Aq Molecules from Autoimmune-prone DBA/1 Mice

Antigen-presenting cells degrade endocytosed antigens, e.g. collagen type II, into peptides that are bound and presented to arthritogenic CD4(+) helper T cells by major histocompatibility complex (MHC) class II molecules. Efficient loading of many MHC class II alleles with peptides requires the assistance of H2-M (HLA-DM in humans), a heterodimeric MHC class II-like molecule that facilitates CLIP removal from MHC class II molecules and aids to shape the peptide repertoire presented by MHC class II to CD4(+) T cells. In contrast to the HLA-DM region in humans, the beta-chain locus is duplicated in mice, with the H2-Mb1 beta-chain distal to H2-Mb2 and the H2-Ma alpha-chain gene. H2-M alleles …

Clonal expansion of melan a-specific cytotoxic T lymphocytes in a melanoma patient responding to continued immunization with melanoma-associated peptides

Peptides derived from human tumor antigens have been used in a number of clinical trials to induce specific immune responses against autologous tumors in cancer patients. Although favorable clinical results were observed in single patients, immune responses correlating with tumor regression were either not detected or in case of responses, the T-cell specificity was difficult to demonstrate. In this study, we analyzed antigen-specific T-cell responses induced in the skin and in peripheral blood lymphocytes (PBL) in an HLA-A2-positive melanoma patient. The patient showed major regression of metastatic melanoma under continued immunization with peptides derived from the melanocyte differentia…

Interleukin-2 and its Receptors in Human Solid Tumours: Immunobiology and Clinical Significance

Human carcinomas were found to express IL-2 R and to produce, but not to secrete, IL-2. Intermediate affinity IL-2Rβγ detected on the surface and in the cytoplasm of carcinoma cells binds exogenous IL-2 at the nanomolar or micromolar concentrations and mediates cell cycle arrest (CCA) possibly through the upregulation of the CDK inhibitor p27kipl expression. In contrast, IL-2Rα is modestly expressed on the cell surface, and it may be involved in the intracrine pathway of delivering endogenous IL-2 to the cell surface. IL-2 is a growth factor for human carcinomas, and as it binds to the high-affinity IL-2R, it promotes cellular proliferation by suppressing expression of p27kipl. It also prot…

Intravascular ultrasound imaging of arterial wall architecture.

Intravascular ultrasound (IVUS) is a promising new technique for assessing vascular morphology and structure. Controversy exists whether the three-layer appearance of the arterial wall correctly reflects the histologic structures of the intima, media, and adventitia. We performed an experimental study to clarify the three-layer appearance. The vessel wall architecture was analyzed by IVUS on eight different kinds of plastic cylinders, 24 normal blood vessels from pigs, and 59 human arterial segments. A distinct three-layer appearance was observed on all the plastic cylinders when the ultrasound beam was perpendicular to the wall. A three-layer appearance was also seen in the arterial wall, …