Classical cardiovascular risk factors according to fasting plasma glucose levels

To compare the prevalence of classical cardiovascular risk factors (CVRF) and metabolic syndrome (MetS) in our population according to fasting plasma glucose levels (FPG).We have studied 344 subjects between 20-70 years of age, recruited in a Primary Care Clinic. Subjects were divided into four groups according to their fasting plasma glucose (FPG) values: normal plasma glucose (NG) when FPG5.6 mmol/L; FPG between 5.6 and 6.0 mmol/L (FPG1); FPG between 6.1-6.9 mmol/L (FPG2); and diabetes (DM) FPGor = 7 mmol/L or previous diagnosis of diabetes. Cardiovascular risk factors (hypertension, TC/HDL-C index and Apo B values), presence of the MetS and indirect measure of insulin resistance (HOMA) w…

T cell assays and MIATA: the essential minimum for maximum impact.

The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA*Correspondence: cedrik.britten@tron-mainz.dehttp://dx.doi.org/10.1016/j.immuni.2012.07.010The field of immunology has recentlyexperienced enormous advances fromwhich most have so far not been incorpo-rated into standard medical practice (Da-vis, 2008). One approach to fully exploitthe existing wealth of knowledge is toimplement a systematic strategy to eval-uate the immune system. The potentialbenefit of such an approach is that itmay lead to results that can be translatedinto the rational development of diagnos-tics and therapeutics (Hoos et al., 2011).Two prerequisites for its application ar…

Cuantificación de insulinorresistencia con los valores de insulina basal e índice HOMA en una población no diabética

Fundamento Calcular la prevalencia y definir el sindrome de insulinorresistencia mediante la determinacion de insulinemia basal y el indice HOMA, y estudiar su relacion con otros componentes del sindrome metabolico. Sujetos y metodo Estudiamos una poblacion de 292 sujetos no diabeticos, de ambos sexos y edades entre 20 y 65 anos, seleccionados por un metodo de muestreo simple aleatorio entre los que consultaron durante un ano en un centro de salud (en el area metropolitana de Valencia), mediante un metodo de busqueda oportunista. De ellos se selecciono a un subgrupo formado por 96 sujetos que no tenian caracteristicas clinicas ni analiticas del sindrome de insulinorresistencia, y se estudia…

Quantitation of antigen-reactive T cells in peripheral blood by IFNgamma-ELISPOT assay and chromium-release assay: a four-centre comparative trial

The ELISPOT assay is increasingly being used for the monitoring of the induction of antigen-reactive T cells in cancer vaccination trials. In order to evaluate the reliability of T cell frequency analysis with the ELISPOT assay, a comparative study was performed in four European laboratories. Six samples from healthy subjects were analyzed for the frequency of influenza-reactive CD8+ T cells in peripheral blood mononuclear cells (PBMC) by IFNgamma-ELISPOT assay. In addition, one laboratory determined cytotoxic T cell precursor (CTL) frequencies in these samples by limiting dilution chromium-release assay (LDA), and three laboratories performed a variant of the LDA, the multiple microculture…

The role of the reporting framework MIATA within current efforts to advance immune monitoring

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 codin…

Consensus nomenclature for CD8(+) T cell phenotypes in cancer

International audience; Whereas preclinical investigations and clinical studies have established that CD8+ T cells can profoundly affect cancer progression, the underlying mechanisms are still elusive. Challenging the prevalent view that the beneficial effect of CD8+ T cells in cancer is solely attributable to their cytotoxic activity, several reports have indicated that the ability of CD8+ T cells to promote tumor regression is dependent on their cytokine secretion profile and their ability to self-renew. Evidence has also shown that the tumor microenvironment can disarm CD8+ T cell immunity, leading to the emergence of dysfunctional CD8+ T cells. The existence of different types of CD8+ T…

Generation of cytotoxic T-cell responses with synthetic melanoma-associated peptidesin vivo: Implications for tumor vaccines with melanoma-associated antigens

Peptide epitopes derived from differentiation antigens of the melanocyte lineage have been identified in human melanomas and normal cultured melanocytes as targets for MHC-restricted cytotoxic T lymphocytes (CTL). Characterization of multiple CTL-defined antigenic determinants and the presence of corresponding precursor CTL open perspectives for the development of antigen-based vaccines. In the present study, we determined the CTL reactivity against melanoma-associated peptides derived from Melan A/MART-1, tyrosinase and gp100/Pmel17 in 10 HLA-A2+ melanoma patients and 10 healthy individuals. Then, we examined the immunological effects and toxicity of intradermal inoculation of synthetic me…

Allorestricted T lymphocytes with a high avidity T-cell receptor towards NY-ESO-1 have potent anti-tumor activity.

The cancer-testis antigen NY-ESO-1 has been targeted as a tumor-associated antigen by immunotherapeutical strategies, such as cancer vaccines. The prerequisite for a T-cell-based therapy is the induction of T cells capable of recognizing the NY-ESO-1-expressing tumor cells. In this study, we generated human T lymphocytes directed against the immunodominant NY-ESO-1(157-165) epitope known to be naturally presented with HLA-A*0201. We succeeded to isolate autorestricted and allorestricted T lymphocytes with low, intermediate or high avidity TCRs against the NY-ESO-1 peptide. The avidity of the established CTL populations correlated with their capacity of lysing HLA-A2-positive, NY-ESO-1-expre…

Cooperation of Human Tumor-Reactive CD4+ and CD8+ T Cells after Redirection of Their Specificity by a High-Affinity p53A2.1-Specific TCR

Abstract Efficient immune attack of malignant disease requires the concerted action of both CD8 + CTL and CD4 + Th cells. We used human leukocyte antigen (HLA)-A*0201 (A2.1) transgenic mice, in which the mouse CD8 molecule cannot efficiently interact with the α3 domain of A2.1, to generate a high-affinity, CD8-independent T cell receptor (TCR) specific for a commonly expressed, tumor-associated cytotoxic T lymphocyte (CTL) epitope derived from the human p53 tumor suppressor protein. Retroviral expression of this CD8-independent, p53-specific TCR into human T cells imparted the CD8 + T lymphocytes with broad tumor-specific CTL activity and turned CD4 + T cells into potent tumor-reactive, p53…

Papel de la dislipemia aterogénica en el desarrollo del síndrome metabólico

Fundamento y objetivo Averiguar si el diagnostico de sindrome metabolico (SM) definido por los criterios de la International Diabetes Federation (IDF) en 2005 identifica a un mayor numero de sujetos con dislipemia aterogenica de elevado riesgo cardiovascular que los criterios del National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP-III). Pacientes y metodo Estudiamos a una poblacion de 344 sujetos no diabeticos (158 varones y 186 mujeres), de edades comprendidas entre 20 y 70 anos, seleccionados por un metodo de muestreo simple aleatorio entre los que consultaron durante un ano en un centro de salud en el area metropolitana de Valencia (metodo de busqueda oportunista).…

“MIATA”—Minimal Information about T Cell Assays

Immunotherapy, especially therapeutic vaccination, has a great deal of potential in the treatment of cancer and certain infectious diseases such as HIV (Allison et al., 2006; Fauci et al., 2008; Feldmann and Steinman, 2005). Numerous vaccine candidates have been tested in patients with a variety of tumor types and chronic viral diseases. Often, the best way to assess the clinical potential of these vaccines is to monitor the induced T cell response, and yet there are currently no standards for reporting these results. This letter is an effort to address this problem.

High frequency of functionally active Melan-a-specific T cells in a patient with progressive immunoproteasome-deficient melanoma.

AbstractTumor-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 t…

Redirection of T cells by delivering a transgenic mouse-derived MDM2 tumor antigen-specific TCR and its humanized derivative is governed by the CD8 coreceptor and affects natural human TCR expression.

Retroviral transfer of T cell antigen receptor (TCR) genes selected by circumventing tolerance to broad tumor- and leukemia-associated antigens in human leukocyte antigen (HLA)-A*0201 (A2.1) transgenic (Tg) mice allows the therapeutic reprogramming of human T lymphocytes. Using a human CD8 x A2.1/Kb mouse derived TCR specific for natural peptide-A2.1 (pA2.1) complexes comprising residues 81-88 of the human homolog of the murine double-minute 2 oncoprotein, MDM2(81-88), we found that the heterodimeric CD8 alpha beta coreceptor, but not normally expressed homodimeric CD8 alpha alpha, is required for tetramer binding and functional redirection of TCR- transduced human T cells. CD8+T cells that…

Abdominal obesity, insulin resistance, and metabolic syndrome in a southern European population.

Background: Our objective was to investigate the relationship between abdominal obesity (AO), as measured by waist circumference (WC), insulin resistance (IR), and components of the metabolic syndrome (MS). Methods: A cross-sectional study was carried out with 283 subjects (130 males and 153 females aged 25–65 years) from a primary care outpatient clinic in Valencia (Spain) over a period of 1 year. Body mass index (BMI), waist circumference (WC), blood pressure (BP), total cholesterol, triglycerides, HDL-C, glucose, and insulin were measured by standard methods. IR was defined as HOMA-IR equal to or greater than 3.8. Results: The prevalence of IR was 39.6%. Subjects were divided into groups…

Harmonization of Immune Biomarker Assays for Clinical Studies

Assays that measure a patient's immune response play an increasingly important role in the development of immunotherapies. The inherent complexity of these assays and independent protocol development between laboratories result in high data variability and poor reproducibility. Quality control through harmonization--based on integration of laboratory-specific protocols with standard operating procedures and assay performance benchmarks--is one way to overcome these limitations. Harmonization guidelines can be widely implemented to address assay performance variables. This process enables objective interpretation and comparison of data across clinical trial sites and also facilitates the ide…

Molecular Design of the Cαβ Interface Favors Specific Pairing of Introduced TCRαβ in Human T Cells

Abstract A promising approach to adoptive transfer therapy of tumors is to reprogram autologous T lymphocytes by TCR gene transfer of defined Ag specificity. An obstacle, however, is the undesired pairing of introduced TCRα- and TCRβ-chains with the endogenous TCR chains. These events vary depending on the individual endogenous TCR and they not only may reduce the levels of cell surface-introduced TCR but also may generate hybrid TCR with unknown Ag specificities. We show that such hybrid heterodimers can be generated even by the pairing of human and mouse TCRα- and TCRβ-chains. To overcome this hurdle, we have identified a pair of amino acid residues in the crystal structure of a TCR that …