BackgroundNatural killer cell cytotoxicity is decreased in patients with acute myeloid leukemia in comparison to that in normal controls. Tumor-derived microvesicles present in patients' sera exert detrimental effects on immune cells and may influence tumor progression. Design and MethodsWe investigated the microvesicle protein level, molecular profile and suppression of natural killer cell activity in patients with newly diagnosed acute myeloid leukemia. ResultsThe patients' sera contained higher levels of microvesicles compared to the levels in controls (P<0.001). Isolated microvesicles had a distinct molecular profile: in addition to conventional microvesicle markers, they contained membrane-associated transforming growth factor-β1, MICA/MICB and myeloid blasts markers, CD34, CD33 and CD117. These microvesicles decreased natural killer cell cytotoxicity (P<0.002) and down-regulated expression of NKG2D in normal natural killer cells (P<0.001). Sera from patients with acute myeloid leukemia contained elevated levels of transforming growth factor-β, and urea-mediated dissociation of microvesicles further increased the levels of this protein. Neutralizing anti-transforming growth factor-β1 antibodies inhibited microvesicle-mediated suppression of natural killer cell activity and NKG2D down-regulation. Interleukin-15 protected natural killer cells from adverse effects of tumor-derived microvesicles. ConclusionsWe provide evidence for the existence in acute myeloid leukemia of a novel mechanism of natural killer cell suppression mediated by tumor-derived microvesicles and for the ability of interleukin-15 to counteract this suppression. factor-β1. Haematologica 2011;96(9):1302-1309. doi:10.3324/haematol.2010 This is an open-access paper.Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor-β1

Purpose Regulatory CD4+CD25highFoxp3+ T cells (Treg) control peripheral immune tolerance. Patients with cancer, including those with hematologic malignancies, have elevated numbers of Treg in the peripheral circulation and in tumor tissues. However, mechanisms of suppression and clinical significance of Treg, especially in patients with acute myelogenous leukemia (AML), has not been well defined. Experimental Design We prospectively evaluated the phenotype, function, and mechanisms of suppression used by Treg in newly diagnosed untreated AML patients. The relationship between the frequency of circulating Treg and the disease status as well as treatment outcome was also evaluated. Results The percentage of circulating Treg was higher (P < 0.0001) and their phenotype was distinct in AML patients relative to normal controls. Suppression mediated by Treg coincubated with proliferating autologous responder cells was also higher (P < 0.001) in AML than that mediated by control Treg. Using Transwell inserts, we showed that interleukin-10 and transforming growth factor-β1 production as well as cell-to-cell contact were necessary for Treg-mediated suppression. Also, the pretreatment Treg frequency predicted response to chemotherapy. Unexpectedly, patients who achieved complete remission still had elevated frequency of Treg, which mediated high levels of suppressor activity. Conclusions Treg accumulating in the peripheral circulation of AML patients mediate vigorous suppression via contact-dependent and contact-independent mechanisms. Patients with lower Treg frequency at diagnosis have a better response to induction chemotherapy. During the post-induction period, the Treg frequency and suppressive activity remain elevated in complete remission, suggesting that Treg are resistant to conventional chemotherapy.

PurposeTo date, few studies have been undertaken to make explicit how microblogging technologies are used by and can benefit scholars. This paper investigates the use of Twitter by an academic community, and poses the following questions: does the use of a Twitter enabled backchannel enhance the conference experience, collaboration and the co-construction of knowledge? How is microblogging used within an academic conference setting, and can we articulate the benefits it may bring to a discipline? Prominent Tweeters were identified and a small qualitative survey was undertaken to ascertain individuals' attitudes towards a Twitter enabled backchannel. Findings Draft for comment2 Conference hashtagged Twitter activity does not constitute a single distributed conversation but, rather multiple monologues with a few intermittent, discontinuous, loosely joined dialogues between users. The digital backchannel constitutes a multidirectional complex space in which the users make notes, share resources, hold discussions and ask questions as well as establishing a clear individual online presence. The use of Twitter as a platform for conference backchannels enables the community to expand communication and participation of events amongst its members. The analysis revealed the close knit nature of the DH researcher community, which may be somewhat intimidating for those new to the field or conference. Practical implicationsThis study has indicated that, given Twitter is becoming increasingly important for academic communities, new, dedicated methodologies for the analysis and understanding of Tweet based corpora are necessary. Routinely used textual analysis tools cannot be applied to corpora of tweets in a straightforward manner, due to the creative and fragmentary nature of language used within microblogging. In this paper, a method has been suggesting to categorize tweets using open coded analysis to facilitate understanding of tweet based corpora, which could be adopted by other studies. Originality/valueThis paper is the first exhaustive study that we are aware of concentrating on how microblogging technologies such as twitter are used by and can benefit scholars. This data set provides both a valuable insight into the prevalence of a variety of Twitter practices within the constraints of a conference setting, and highlights the need for methodologies to be developed to analyse social media streams such as twitter feeds. It also provides a comprehensive bibliography of other research into microblogging.

Interleukin-15 (IL-15) has a major role in NK-cell homeostasis. Modulation of the relative frequency and expression intensity of the NK-cell receptors by IL-15 may increase NK cell-mediated cytotoxicity in cancer patients. We investigated the receptor repertoire and measured NK-cell activity in newly diagnosed AML patients and evaluated the ex vivo effects of IL-15. The expression of the activating NK cell receptors was significantly decreased in the AML patients compared to that in NK cells of healthy donors. When NK cells obtained from AML patients were cultured with IL-15, expression of the activating receptors was significantly upregulated compared to pre-culture levels. Concomitantly, cytotoxic activity of NK cells against autologous leukemic blasts increased following IL-15 stimulation. This IL-15 induced increase in activity was blocked by neutralizing antibodies specific for the NK cell activating receptors. These pre-clinical data support the future use of IL-15 for NK cell-based therapies for AML patients.

BACKGROUND: Since 1975, there has been a dramatic increase in the survival rates of pediatric and older cancer patients, but adolescent and young adult (AYA) patients ages 15 to 40 years have not had a similar improvement. Data indicate a direct correlation between increased cure rates and clinical trial enrollment. METHODS: The authors previously published data indicating inferior clinical trial enrollment when AYA patients were treated at an adult oncology center versus a pediatric oncology center. To address this deficit, a joint pediatric and adult AYA Oncology Program was established in July 2006 with the primary objective of improving outcomes by increasing therapeutic clinical trial enrollment in this population. Patients who were referred to that program from July 2006 through June 2010 were examined retrospectively to establish whether clinical trial enrollment increased compared with historic controls. RESULTS: Fifty-seven patients were referred to the program from 2006 to 2010 (range, 12-16 new patients per year). Eight patients were referred for consultation only and were not treated at the University of Pittsburgh Cancer Institute or Children's Hospital of Pittsburgh. Five of 22 patients (23%) who received treatment at the pediatric cancer center were enrolled onto a clinical trial, whereas 9 of 27 patients (33%) patients who received treatment at the adult cancer center were enrolled. There was superior trial participation compared with the previous 3 years for those shared AYA patients who were treated at the adult center (P < .001). CONCLUSIONS: Data from this study demonstrated that establishing a unified AYA oncology program can lead to improved clinical trial enrollment for patients who are treated at medical oncology centers. Cancer 2012;118:3614-