Interleukin-21 can efficiently restore impaired antibody-dependent cell-mediated cytotoxicity in patients with oesophageal squamous cell carcinoma.
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ABSTRACT:
SUBMITTER: Watanabe M
PROVIDER: S-EPMC2822939 | biostudies-other | 2010 Feb
REPOSITORIES: biostudies-other
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Project description:BackgroundQualitative and quantitative defects in natural killer (NK) cells have been noted in patients with acute myeloid leukemia (AML), providing rationale for infusion of donor-derived NK cells. We previously showed that decitabine enhances expression of NKG2D ligands in AML with additive cytotoxicity when NK cells and Fc (fragment crystallizable region)-engineered CD33 monoclonal antibody (CD33mAb) was used. We conducted a phase 1 study evaluating decitabine and haploidentical NK cells in relapsed AML. Using patient samples from this study, we evaluated whether ex vivo donor-derived expanded NK cells with or without CD33mAb was effective in decitabine-treated AML.MethodsBone marrow aspirates were collected from patients at pre- and post-NK cell infusion. NK cells from healthy donors were expanded for 14 days using irradiated K562 feeder cells displaying membrane-bound IL-21 (mbIL-21). Patient samples were used to test in vitro activity of mbIL-21 NK cells ± CD33m Ab-dependent cellular cytotoxicity (ADCC) and AML patient derived xenograft (PDX) mice were developed to test in vivo activity.ResultsUpon incubation with primary AML blasts, mbIL-21 NK cells showed variable donor-dependent intra-cellular interferon-γ production, which increased with CD33mAb-coated AML. ADCC assays revealed mbIL-21 NK cells effectively lysed primary AML blasts with higher activity on CD33mAb-coated AML. Importantly, CD33mAb-dependent enhanced cytotoxicity by mbIL-21 NK cells was maintained in AML cells from patients even 24 days post-decitabine treatment. In vivo infusion of mbIL-21 NK cells in AML PDX mice, treated with CD33mAb, reduced the tumor burden.DiscussionThese data show the therapeutic utility of mbIL-21 NK cells that can be further potentiated by addition of CD33mAb in AML.
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Project description:BackgroundMicrobiota has been reported to play a role in cancer patients. Nevertheless, little is known about the association between alcohol consumption and resultant changes in the diversity and composition of oesophageal microbiota in oesophageal squamous cell carcinoma (ESCC).MethodsWe performed a hospital-based retrospective study of 120 patients with pathologically diagnosed primary ESCC. The relevant information for all study participants were collected through a detailed questionnaire. The differences in adjacent tissues between non-drinkers and drinkers were explored using 16S rRNA gene sequencing. Raw sequencing data were imported into QIIME 2 to analyse the diversity and abundance of microbiota. Linear discriminant analysis effect size (LEfSe) and unconditional logistic regression were performed to determine the bacterial taxa that were associated with drinking.ResultsThe Shannon diversity index and Bray-Curtis distance of oesophageal microbiota were significantly different among drinkers(P < 0.05). The alcohol-related bacteria were primarily from the orders Clostridiales, Gemellales and Pasteurellales, family Clostridiaceae, Lanchnospiraceae, Helicobacteraceae, Alcaligenaceae, Bacteroidaceae, Pasteurellaceae and Gemellaceae; genus Clostridium, Helicobacter, Catonella, Bacteroides, Bacillus, Moraxella, and Bulleidia; and species B. moorei and longum (genus Bifidobacterium). In addition, the diversity and abundance of these microbiota were observed to be affected by the age, residential districts of the patients, and sampling seasons. Moreover, the higher the frequency and years of alcohol consumption, the lower was the relative abundance of genus Catonella that was observed.ConclusionAlcohol consumption is associated with alterations in both the diversity and composition the of the oesophageal microbiota in ESCC patients.
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