Browsing by Subject "SUBSET"

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  • Ekman, Ilse; Ihantola, Emmi-Leena; Viisanen, Tyyne; Rao, Deepak A.; Näntö-Salonen, Kirsti; Knip, Mikael; Veijola, Riitta; Toppari, Jorma; Ilonen, Jorma; Kinnunen, Tuure (2019)
    Aims/hypothesis Type 1 diabetes is preceded by a period of asymptomatic autoimmunity characterised by positivity for islet autoantibodies. Therefore, T helper cell responses that induce B cell activation are likely to play a critical role in the disease process. Here, we aimed to evaluate the role of a recently described subset, C-X-C motif chemokine receptor type 5-negative, programmed cell death protein 1-positive (CXCR5(-)PD-1(hi)) peripheral T helper (Tph) cells, in human type 1 diabetes. Methods The phenotype of blood CXCR5(-)PD-1(hi) CD4(+) T cells was analysed by multicolour flow cytometry. The frequencies of circulating CXCR5(-)PD-1(hi) T cells were analysed in a cohort of 44 children with newly diagnosed type 1 diabetes, 40 autoantibody-positive (AAb(+)) at-risk children and 84 autoantibody-negative healthy control children, and the findings were replicated in a separate cohort of 15 children with newly diagnosed type 1 diabetes and 15 healthy control children. Results Circulating CXCR5(-)PD-1(hi) Tph cells share several features associated with B cell helper function with circulating CXCR5(+)PD-1(hi) follicular T helper (Tfh) cells. Moreover, the frequency of circulating Tph cells was increased in children with newly diagnosed type 1 diabetes, especially in those who are positive for multiple autoantibodies. Importantly, circulating Tph cells were also increased in autoantibody-positive at-risk children who later progressed to type 1 diabetes. Conclusions/interpretation Our results demonstrate that circulating CXCR5(-)PD-1(hi) Tph cells are associated with progression to clinical type 1 diabetes. Consequently, Tph cells could have potential both as a biomarker of disease progression and as a target for immunotherapy in type 1 diabetes.
  • Demetri, G. D.; Antonescu, C. R.; Bjerkehagen, B.; Bovee, J. V. M. G.; Boye, K.; Chacon, M.; Dei Tos, A. P.; Desai, J.; Fletcher, J. A.; Gelderblom, H.; George, S.; Gronchi, A.; Haas, R. L.; Hindi, N.; Hohenberger, P.; Joensuu, H.; Jones, R. L.; Judson, Ian; Kang, Y-K; Kawai, A.; Lazar, A. J.; Le Cesne, A.; Maestro, R.; Maki, Rg; Martin, J.; Patel, S.; Penault-Llorca, F.; Raut, C. Premanand; Rutkowski, P.; Safwat, A.; Sbaraglia, M.; Schaefer, I-M; Shen, L.; Serrano, C.; Schoffski, P.; Stacchiotti, S.; Hall, K. Sundby; Tap, W. D.; Thomas, D. M.; Trent, J.; Valverde, C.; van der Graaf, W. T. A.; von Mehren, M.; Wagner, A.; Wardelmann, E.; Naito, Y.; Zalcberg, J.; Blay, J-Y (2020)
    Sarcomas are a heterogeneous group of malignancies with mesenchymal lineage differentiation. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as tissue-agnostic oncogenic drivers has led to new personalized therapies for a subset of patients with sarcoma in the form of tropomyosin receptor kinase (TRK) inhibitors. NTRK gene rearrangements and fusion transcripts can be detected with different molecular pathology techniques, while TRK protein expression can be demonstrated with immunohistochemistry. The rarity and diagnostic complexity of NTRK gene fusions raise a number of questions and challenges for clinicians. To address these challenges, the World Sarcoma Network convened two meetings of expert adult oncologists and pathologists and subsequently developed this article to provide practical guidance on the management of patients with sarcoma harboring NTRK gene fusions. We propose a diagnostic strategy that considers disease stage and histologic and molecular subtypes to facilitate routine testing for TRK expression and subsequent testing for NTRK gene fusions.
  • Borssen, Magnus; Haider, Zahra; Landfors, Mattias; Noren-Nystrom, Ulrika; Schmiegelow, Kjeld; Asberg, Ann E.; Kanerva, Jukka; Madsen, Hans O.; Marquart, Hanne; Heyman, Mats; Hultdin, Magnus; Roos, Goran; Forestier, Erik; Degerman, Sofie (2016)
    Background. Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects. In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T-ALL. Procedure. Sixty-five diagnostic T-ALL samples from Nordic pediatric patients treated according to the Nordic Society of Pediatric Hematology and Oncology ALL 2008 (NOPHO ALL 2008) protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation to clinical data and early T-cell precursor (ETP) phenotype. Results. Two distinct CpG island methylator phenotype (CIMP) groups were identified. Patients with a CIMP-negative profile had an inferior response to treatment compared to CIMP-positive patients (3-year cumulative incidence of relapse (CIR3y) rate: 29% vs. 6%, P = 0.01). Most importantly, CIMP classification at diagnosis allowed subgrouping of high-risk T-ALL patients (MRD >= 0.1% at day 29) into two groups with significant differences in outcome (CIR3y rates: CIMP negative 50% vs. CIMP positive 12%; P = 0.02). These groups did not differ regarding ETP phenotype, but the CIMP-negative group was younger (P = 0.02) and had higher white blood cell count at diagnosis (P = 0.004) compared with the CIMP-positive group. Conclusions. CIMP classification at diagnosis in combination with MRD during induction therapy is a strong candidate for further risk classification and could confer important information in treatment decision making. (C) 2016 Wiley Periodicals, Inc.
  • Marquardt, Nicole; Kekalainen, Eliisa; Chen, Puran; Lourda, Magda; Wilson, Jennifer N.; Scharenberg, Marlena; Bergman, Per; Al-Ameri, Mamdoh; Hard, Joanna; Mold, Jeffrey E.; Ljunggren, Hans-Gustaf; Michaelsson, Jakob (2019)
    Human lung tissue-resident NK cells (trNK cells) are likely to play an important role in host responses towards viral infections, inflammatory conditions and cancer. However, detailed insights into these cells are still largely lacking. Here we show, using RNA sequencing and flow cytometry-based analyses, that subsets of human lung CD69(-)CD16(-) NK cells display hallmarks of tissue-residency, including high expression of CD49a, CD103, and ZNF683, and reduced expression of SELL, S1PR5, and KLF2/3. CD49a(+)CD16(-) NK cells are functionally competent, and produce IFN-gamma, TNF, MIP-1 beta, and GM-CSF. After stimulation with IL-15, they upregulate perforin, granzyme B, and Ki67 to a similar degree as CD49a(-) CD16(-) NK cells. Comparing datasets from trNK cells in human lung and bone marrow with tissue-resident memory CD8(+) T cells identifies core genes co-regulated either by tissue-residency, cell-type or location. Together, our data indicate that human lung trNK cells have distinct features, likely regulating their function in barrier immunity.