Search results for "TUMOR"
showing 10 items of 6365 documents
Polyphosphate as a donor of high-energy phosphate for the synthesis of ADP and ATP.
2017
Here, we studied the potential role of inorganic polyphosphate (polyP) as an energy source for ADP and ATP formation in the extracellular space. In SaOS-2 cells, we show that matrix vesicles are released into the extracellular space after incubation with polyP. These vesicles contain both alkaline phosphatase (ALP) and adenylate kinase (AK) activities (mediated by ALPL and AK1 enzymes). Both enzymes translocate to the cell membrane in response to polyP. To distinguish the process(es) of AMP and ADP formation during ALP hydrolysis from the ATP generated via the AK reaction, inhibition studies with the AK inhibitor A(5')P5(5')A were performed. We found that ADP formation in the extracellular …
Tumor-priming converts NK cells to memory-like NK cells
2017
Fascinating earlier evidence suggests an intrinsic capacity of human natural killer (NK) cells to acquire adaptive immune features in the context of cytomegalovirus (CMV) infection or pro-inflammatory cytokine stimulation. Since the role of memory NK cells in cancer has so far remained elusive and adoptive NK cell transfer in relapsing pediatric acute B cell precursor leukemia (BCP-ALL) patients awaits improvement, we asked the question whether tumor-priming could promote the generation of memory NK cells with enhanced graft-vs.-leukemia (GvL) reactivity. Here, we provide substantial evidence that priming of naive human NK cells with pediatric acute B cell leukemia or acute myeloid leukemia…
Mutanome directed cancer immunotherapy
2015
Somatic mutations are important drivers of cancer development. Accumulating evidence suggests that a significant subset of mutations result in neo-epitopes recognized by autologous T cells and thus may constitute the Achilles' heel of tumor cells. T cells directed against mutations have been shown to have a key role in clinical efficacy of potent cancer immunotherapy modalities, such as adoptive transfer of autologous tumor infiltrating lymphocytes and immune checkpoint inhibitors. Whereas these findings strengthen the idea of a prominent role of neo-epitopes in tumor rejection, the systematic therapeutic exploitation of mutations was hampered until recently by the uniqueness of the reperto…
γδ cells and tumor microenvironment: A helpful or a dangerous liason?
2017
Abstract γδ T cells are a subset of T lymphocytes that have been implicated in immunosurveillance against infections and tumors. γδ T cells are endowed with antitumor activities, and hence several γδ T cell-based small-scale clinical trials have been conducted either by in vivo activation by intravenous administration of aminobiphosphonates or by adoptive transfer of in vitro expanded γδ T cells. Although both these strategies have yielded promising results, there are a number of limitations associated with each of them which, if overcome may help to further improve efficacy. One of the most important limits is the possible polarization of tumor-infiltrating γδ T cells toward different γδ T…
γδ cell-based immunotherapy for cancer.
2019
Introduction: Cancer immunotherapy relies on the development of an efficient and long-lasting anti-tumor response, generally mediated by cytotoxic T cells. gamma delta T cells possess distinctive features that justify their use in cancer immunotherapy. Areas covered: Here we will review our current knowledge on the functions of human gamma delta T cells that may be relevant in tumor immunity and the most recent advances in our understanding of how these functions are regulated in the tumor microenvironment. We will also discuss the major achievements and limitations of gamma delta T cell-based immunotherapy of cancer. Expert opinion: Several small-scale clinical trials have been conducted i…
Prox1 Is Required for Oligodendrocyte Cell Identity in Adult Neural Stem Cells of the Subventricular Zone
2016
Abstract Adult neural stem cells with the ability to generate neurons and glia cells are active throughout life in both the dentate gyrus (DG) and the subventricular zone (SVZ). Differentiation of adult neural stem cells is induced by cell fate determinants like the transcription factor Prox1. Evidence has been provided for a function of Prox1 as an inducer of neuronal differentiation within the DG. We now show that within the SVZ Prox1 induces differentiation into oligodendrocytes. Moreover, we find that loss of Prox1 expression in vivo reduces cell migration into the corpus callosum, where the few Prox1 deficient SVZ-derived remaining cells fail to differentiate into oligodendrocytes. Thu…
Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced…
2019
Abstract Purpose: IDO1 induces immune suppression in T cells through l-tryptophan (Trp) depletion and kynurenine (Kyn) accumulation in the local tumor microenvironment, suppressing effector T cells and hyperactivating regulatory T cells (Treg). Navoximod is an investigational small-molecule inhibitor of IDO1. This phase I study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of navoximod in combination with atezolizumab, a PD-L1 inhibitor, in patients with advanced cancer. Patients and Methods: The study consisted of a 3+3 dose-escalation stage (n = 66) and a tumor-specific expansion stage (n = 92). Navoximod was given orally every 12 hours continuously for 21 consecu…
Dynamic clonal remodelling in breast cancer metastases is associated with subtype conversion
2019
Background: Changes in the clinical subtype (CS) and intrinsic subtype (IS) between breast cancer (BC) metastases and corresponding primary tumours have been reported. However, their relationship with tumour genomic changes remains poorly characterised. Here, we analysed the association between genomic remodelling and subtype conversion in paired primary and metastatic BC samples. Methods: A total of 57 paired primary and metastatic tumours from GEICAM/2009-03 (ConvertHER, NCT01377363) study participants with centrally assessed CS (n = 57) and IS (n = 46) were analysed. Targeted capture and next-generation sequencing of 202 genes on formalin-fixed paraffin-embedded samples was performed. Th…
Immunosuppressive profiles in liquid biopsy at diagnosis predict response to neoadjuvant chemotherapy in triple-negative breast cancer.
2020
Background: Triple-negative breast cancer (TNBC) is characterised by high pathological complete response to neoadjuvant chemotherapy (NAC). However, refractory and poor NAC responders still face very poor outcome, emphasising the urgent need for tools that facilitate identification of these patients, so that surgery or alternatives to NAC are considered early in the treatment protocol. Materials and methods: We combined metabolomics, exosome circulating miRNAs and flow cytometry experimental approaches in TNBC patients at diagnosis with immunohistochemistry in needle biopsy tumours to generate NAC-response predictive models. We also co-cultured and studied crosstalk between isolated patient…
Genome-wide DNA methylation differences according to oestrogen receptor beta status in colorectal cancer.
2019
Involvement of sex hormones in colorectal cancer (CRC) development has been linked to oestrogen receptor β (ERβ). Expression of ERβ is found reduced in tumour tissue and inversely related to mortality. However, mechanisms are not well understood. Our study aimed to detect differentially methylated genes associated with ERβ expression, which could point to mechanisms by which ERβ could influence risk and prognosis of CRC. Epigenome-wide DNA methylation profiling was performed using Illumina HumanMethylation450k BeadChip arrays in two independent tumour sample sets of CRC patients recruited in 2003–2010 by the German DACHS study (discovery cohort n = 917, replication cohort n = 907). ERβ expr…