ABSTRACT
Ligands of the natural killer group 2D (NKG2DL) family are expressed on malignant cells and are usually absent from healthy tissues. Recognition of NKG2DLs such as MICA/B and ULBP1-3 by the activating immunoreceptor NKG2D, expressed by NK and cytotoxic T cells, stimulates anti-tumor immunity in breast cancer. Upregulation of membrane-bound NKG2DLs in breast cancer has been demonstrated by immunohistochemistry. Tumor cells release NKG2DLs via proteolytic cleavage as soluble (s)NKG2DLs, which allows for effective immune escape and is associated with poor prognosis. In this study, we collected serum from 140 breast cancer (BC) and 20 ductal carcinoma in situ (DCIS) patients at the time of initial diagnosis and 20 healthy volunteers (HVs). Serum levels of sNKG2DLs were quantified through the use of ELISA and correlated with clinical data. The analyzed sNKG2DLs were low to absent in HVs and significantly higher in BC patients. For some of the ligands analyzed, higher sNKG2DLs serum levels were associated with the classification of malignant tumor (TNM) stage and grading. Low sMICA serum levels were associated with significantly longer progression-free (PFS) and overall survival (OS). In conclusion, we provide the first insights into sNKG2DLs in BC patients and suggest their potential role in tumor immune escape in breast cancer. Furthermore, our observations suggest that serum sMICA levels may serve as a prognostic parameter in the patients analyzed in this study.
Subject(s)
Breast Neoplasms , Carcinoma, Intraductal, Noninfiltrating , Humans , Female , Research Personnel , Enzyme-Linked Immunosorbent Assay , Health StatusABSTRACT
Despite recent advances in immunophenotyping, the prognosis of acute myeloid leukemia (AML) is still mainly estimated using age and genetic markers. As the genetic heterogeneity of AML patients is high, flow cytometry-based classification with appropriate biomarkers can efficiently complement risk stratification and treatment selection. An increased expression of B7-H3 (CD276), an immune checkpoint protein, has been reported and associated with poor prognosis. However, the available data are limited and heterogeneous. Here, we used a novel, proprietary murine anti-B7-H3 8H8 antibody for the flow cytometric analysis of B7-H3 expression in AML blasts from 77 patients. Our antibody reliably detected substantial B7-H3 expression in 62.3% of AML patients. B7-H3 expression was higher in the monocytic French-American-British (FAB) M5 group and in intermediate and poor risk patients according to the European Leukemia Network. Using receiver operating characteristics (ROCs), we identified a specific fluorescence intensity cut-off of 4.45 to discriminate between B7-H3high and B7-H3low expression. High B7-H3 expression was associated with shorter overall survival (OS) and progression-free survival (PFS). In conclusion, we have developed a novel B7-H3 antibody that serves as a new tool for the detection of B7-H3 expression in AML and may help to facilitate risk stratification and treatment selection in AML patients.
ABSTRACT
AIMS: Transition from pediatric to adult care is difficult for patients with chronic diseases. In this study, factors associated with metabolic control in childhood-onset type 1 diabetes (T1D) after transfer to adult care were analyzed. METHODS: Overall, 224 persons with T1D were contacted yearly from 1998 to 2019. They voluntarily answered a questionnaire about their current hemoglobin A1c (HbA1c) levels, diabetes-associated complications, kind of care, living conditions, and family situation. Then, mixed longitudinal-cross-sectional analyses were carried out. RESULTS: Overall, 190 patients answered at least once (mean age: 26.6 years). Diabetes complications were mentioned by 10 patients (5 microalbuminuria, 5 retinopathy). Most patients (92.6%) were in diabetes-specific care during the first year after transfer, with a trend to leave diabetes-specific care during the observation period. Patients in diabetes-specific care displayed lower HbA1c levels (%/mmol/mol) (7.1/54 vs. 7.5/58). An important predictor for HbA1c after transfer was HbA1c during the year before transfer (r=0.67, p <0.001). Patients living alone showed no difference in HbA1c levels from those living with their parents. Married patients had lower HbA1c levels (7.0/53 vs. 7.3/56, p<0.05) than unmarried ones. Patients with children (15.8%) presented lower HbA1c levels (6.9/52 vs. 7.3/56, p <0.01) than those without. CONCLUSIONS: Good metabolic results are favored in patients followed-up in specialized care, are married, and are parents. We recommend transfer to a diabetologist with experience in T1D at an individual age.