Clinical implication of HLA class I expression in breast cancer

<p>Abstract</p> <p>Background</p> <p>Human leukocyte antigen (HLA)-class I molecules on tumor cells have been regarded as crucial sites where cytotoxic T lymphocytes (CTL) can recognize tumor-specific antigens and are strongly associated with anti-tumor activity. However, the clinical impact of HLA class I expression in breast cancer has not been clarified.</p> <p>Methods</p> <p>A total of 212 breast cancer patients who received curative surgery from 1993 to 2003 were enrolled in the current study. HLA class I expression was examined immunohistochemically using an anti-HLA class I monoclonal antibody. The correlation between HLA class I positivity and clinical factors was analyzed.</p> <p>Results</p> <p>The downregulation of HLA class I expression in breast cancer was observed in 69 patients (32.5%). HLA class I downregulation was significantly associated with nodal involvement (p < 0.05), TNM stage (p < 0.05), lymphatic invasion (p < 0.01), and venous invasion (p < 0.05). Patients with preserved HLA class I had significantly better disease-free interval (DFI) than those with loss of HLA class I (p < 0.05). However, in multivariable analysis, HLA class I was not selected as one of the independent prognostic factors of disease-free interval.</p> <p>Conclusion</p> <p>The examination of HLA class I expression is useful for the prediction of tumor progression and recurrent risk of breast cancer via the antitumor immune system.</p

Do soil carbon sequestration and soil fertility increase by including a gramineous cover crop in continuous soybean?

Cover cropping is a farming practice that may improve C sequestration and soil fertility, but these effects can vary under different edaphoclimatic conditions. The effects of including a winter gramineous cover crop (CC) in continuous soybeans were evaluated in three long-term experiments (8 yr) on one coarse-textured soil and two finetextured soils in the Pampas region of Argentina. The impacts of CC on soil C sequestration, soil nutrient availability, soil organic C (SOC), and N contents of soil particle size fractions were also determined. The inclusion of CC only increased SOC stock by 3.1 Mg ha-1 in the coarse-textured soil (CTS). The labile C fraction in the 0–5-cm depth increased in both the CTS and the fine-textured soils (FTS) by 263% and 93%, respectively. Soil N also increased in the labile fraction by 119% and 112% when a CC was used in the CTS and FTS soils, respectively. Moreover, the inclusion of a CC decreased soil P availability in one experiment (4.9 kg ha-1) and increased soil manganese in two experiments (11 kg ha-1 on average). The inclusion of a gramineous CC in a soybean monoculture increased the C balance, particularly in coarse-textured soils. Considering that soil N was similarly affected, the C/N ratio was not impacted.Fil: Beltran, Marcelo Javier. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Suelos; ArgentinaFil: Galantini, Juan Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Salvagiotti, Fernando. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; ArgentinaFil: Tognetti, Pedro M. Universidad de Buenos Aires. Facultad de Agronomía. IFEVA; Argentina.Fil: Bacigaluppo, Silvina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; ArgentinaFil: Sainz Rozas, Hernan Rene. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Barroco, Mirian. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria General Villegas; Argentina.Fil: Barbieri, Pablo Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce. Unidad Integrada. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Association analysis of human leukocyte antigen class II (DRB1) alleles with leprosy in individuals from São Luís, state of Maranhão, Brazil

Epidemiological studies have demonstrated that the variability of the clinical response to infection caused by Mycobacterium leprae is associated with host genetic factors. The present study investigated the frequency of human leukocyte antigen (HLA) class II (DRB1) alleles in patients with leprosy from São Luís, Maranhão, Brazil. A case-control study was performed in 85 individuals with leprosy and 85 healthy subjects. All samples were analysed via polymerase chain reaction-sequence specific oligonucleotide probes. The HLA-DRB1*16 allele showed a higher frequency in the group with leprosy [(9.41% vs. 4.12%) odds ratio (OR) = 2.41 95% confidence interval (CI) (0.96-6.08) p = 0.05], whereas the HLA-DRB1*11 allele was less frequent in the group with leprosy [(6.47% vs. 11.76%) OR = 0.51 95% CI (0.23-1.12) p = 0.09]. The frequency of HLA-DRB1* alleles between the control group and leprosy patient subgroups presenting different forms of the disease showed that the HLA-DRB1*16 (16.13% vs. 8.24%, OR = 4.10, CI = 1.27-13.27, p = 0.010) and HLA-DRB1*14 (5% vs. 3.53%, OR = 4.63, CI = 1.00-21.08, p = 0.032) alleles were significantly more frequent in patients with different clinical subtypes of leprosy. The sample size was a limitation in this study. Nevertheless, the results demonstrated the existence of a genetic susceptibility associated with the clinical forms of leprosy. The low frequency of the HLA-DRB1*11 allele should be further studied to investigate the possible protective effect of this allele

The MICA-129Met/Val dimorphism affects plasma membrane expression and shedding of the NKG2D ligand MICA.

The MHC class I chain-related molecule A (MICA) is a ligand for the activating natural killer (NK) cell receptor NKG2D. A polymorphism causing a valine to methionine exchange at position 129 affects binding to NKG2D, cytotoxicity, interferon-γ release by NK cells and activation of CD8(+) T cells. It is known that tumors can escape NKG2D-mediated immune surveillance by proteolytic shedding of MICA. Therefore, we investigated whether this polymorphism affects plasma membrane expression (pmMICA) and shedding of MICA. Expression of pmMICA was higher in a panel of tumor (n = 16, P = 0.0699) and melanoma cell lines (n = 13, P = 0.0429) carrying the MICA-129Val/Val genotype. MICA-129Val homozygous melanoma cell lines released more soluble MICA (sMICA) by shedding (P = 0.0015). MICA-129Met or MICA-129Val isoforms differing only in this amino acid were expressed in the MICA-negative melanoma cell line Malme, and clones with similar pmMICA expression intensity were selected. The MICA-129Met clones released more sMICA (P = 0.0006), and a higher proportion of the MICA-129Met than the MICA-129Val variant was retained in intracellular compartments (P = 0.0199). The MICA-129Met clones also expressed more MICA messenger RNA (P = 0.0047). The latter phenotype was also observed in mouse L cells transfected with the MICA expression constructs (P = 0.0212). In conclusion, the MICA-129Met/Val dimorphism affects the expression density of MICA on the plasma membrane. More of the MICA-129Met variants were retained intracellularly. If expressed at the cell surface, the MICA-129Met isoform was more susceptible to shedding. Both processes appear to limit the cell surface expression of MICA-129Met variants that have a high binding avidity to NKG2D.peerReviewe