133 research outputs found
IL15 induces a potent antitumor activity in NK cells isolated from malignant pleural effusions and overcomes the inhibitory effect of pleural fluid
No full textNatural Killer (NK) cells are capable of recognizing and killing cancer cells and play an important role in tumor immunosurveillance. However, tumor-infiltrating NK cells are frequently impaired in their functional capability. A remarkable exception is represented by NK cells isolated from malignant pleural effusions (PE) that are not anergic and, upon IL2-induced activation, efficiently kill tumor cells. Although IL2 is used in various clinical trials, severe side effects may occur in treated patients. In this study, we investigated whether also other clinical-grade cytokines could induce strong cytotoxicity in NK cells isolated from pleural fluid of patients with primary or metastatic tumors of different origins. We show that PE-NK cells, cultured for short-time intervals with IL15, maintain the CD56brightphenotype, a high expression of the main activating receptors, produce cytokines and kill tumor cells in vitro similarly to those treated with IL2. Moreover, IL15-activated PE-NK cells could greatly reduce the growth of established tumors in mice. This in vivo antitumor effect correlated with the ability of IL15-activated PE-NK cells to traffic from periphery to the tumor site. Finally, we show that IL15 can counteract the inhibitory effect of the tumor pleural microenvironment. Our study suggests that IL15-activated NK cells isolated from pleural fluid (otherwise discarded after thoracentesis) may represent a suitable source of effector cells to be used in adoptive immunotherapy of cancer
Identification of diverse innate lymphoid cells in human decidua.
No full textInnate lymphoid cells (ILCs) are developmentally related cells that play an important role in innate defenses and tissue remodeling. So far, only natural killer (NK) cells have been identified and functionally characterized in human decidua where they contribute to induction of immune suppression, neo-angiogenesis, and tissue building/remodeling. The presence of other ILC subsets in human decidua has not been yet characterized. Here we identify in human decidua, during early pregnancy, two subsets of decidual group 3 ILC (ILC3), including lymphoid tissue inducer (LTi)-like cells and natural cytotoxicity receptors (NCRs)(+)ILC3 and interferon-(IFN)γ-producing ILC1, different from NK cells. Decidual LTi-like cells produced interleukin -17 (IL-17) and tumor necrosis factor (TNF), while NCR(+)ILC3 released IL-22 and IL-8. Importantly, NCR(+)ILC3 and LTi-like cells established functional interactions with stromal cells. Decidual LTi-like cells differentiated into NCR(+)ILC3, whereas they marginally contributed to NK cell generation. Our data suggest that decidual ILC3 may play a role in innate defenses and in vessel and tissue building, thus contributing to maintenance of pregnancy.Mucosal Immunology advance online publication, 23 July 2014; doi:10.1038/mi.2014.63
Primary Undifferentiated Large Cell Carcinoma of the Lacrimal Gland
No full textPurpose To report a unique case of primary undifferentiated large cell carcinoma (LCCA) of the lacrimal gland, a tumor not previously described in the ophthalmic literature. Design Single interventional case report. Participants A patient affected by undifferentiated LCCA of the lacrimal gland. Methods A 65-year-old white man with a 3-month history of a painful mass in the left lacrimal gland fossa underwent an incisional biopsy that revealed a "high-grade" epithelial malignancy. Systemic workup revealed enlargement of the regional lymph nodes, and subsequently the patient underwent extended exenteration with clear histologic margins and radical neck lymphadenectomy followed by adjunctive radiotherapy. Fifteen months postoperatively, the patient is alive and well without evidence of local recurrence or metastatic disease. Main Outcome Measures Treatment result, evidence of local recurrences or distant metastasis, and follow-up. Results Histologic examination revealed a poorly circumscribed tumor composed of large cells invading orbital fat, lateral rectus muscle, and peripheral nerves. The surrounding orbital bone was infiltrated, but the surgical margins were clear. The cell population was composed of large cells (>30 μm) with eosinophilic cytoplasm and ovoid and irregular nuclei containing a prominent nucleoli and coarse chromatin. The cell borders were well defined. Mitosis figures were abundant, and Ki-67 was positive in more than 60% of the cells. The cells were arranged in cords and trabeculae or irregular sheets of discohesive cells. The immunophenotype analysis showed positivity for cytokeratin but negative cytokeratin 20 stains, which is considered a distinctive feature of LCCA. Conclusions Undifferentiated LCCAs are rare tumors of the major salivary glands, especially the parotid gland. Primary undifferentiated LCCA of the lacrimal gland has never been reported in the literature. Differential diagnosis must include a primary source in another organ. Given the aggressive nature of the tumor, radical surgery followed by radiotherapy is recommended, but evidence-based indications regarding the preferred line of treatment are lacking and the prognosis remains guarded. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.Fil: Bernardini, Francesco P.. Ospedale Evangelico Internazionale; ItaliaFil: Croxatto, Juan Oscar. Fundación Oftalmología Argentina "J. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bandelloni, Roberto. No especifíca
Stromal cells from human decidua exert a strong inhibitory effect on NK cell function and dendritic cell differentiation.
No full textStromal cells (SC) are an important component of decidual tissues where they are in strict proximity with both NK and CD14(+) myelomonocytic cells that play a role in the maintenance of pregnancy. In this study we analyzed whether decidual SC (DSC) could exert a regulatory role on NK and CD14(+) cells that migrate from peripheral blood (PB) to decidua during pregnancy. We show that DSCs inhibit the IL15-mediated up-regulation of major activating NK receptors in PB-derived NK cells. In addition, the IL15-induced NK cell proliferation, cytolytic activity and IFN-γ production were severely impaired. DSCs sharply inhibited dendritic cells differentiation and their ability to induce allogeneic T cell proliferation. Indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2) mediated the inhibitory effect of DSCs. Our results strongly suggest an important role of DSCs in preventing potentially dangerous immune response, thus contributing to maintenance of pregnancy
NK cells and other innate lymphoid cells in hematopoietic stem cell transplantation
No full textNatural killer (NK) cells play a major role in the T-cell depleted haploidentical hematopoietic stem cell transplantation (haplo-HSCT) to cure high-risk leukemias. NK cells belong to the expanding family of innate lymphoid cells (ILCs). At variance with NK cells, the other ILC populations (ILC1/2/3) are non-cytolytic, while they secrete different patterns of cytokines. ILCs provide host defenses against viruses, bacteria, and parasites, drive lymphoid organogenesis, and contribute to tissue remodeling. In haplo-HSCT patients, the extensive T-cell depletion is required to prevent graft-versus-host disease (GvHD) but increases risks of developing a wide range of life-threatening infections. However, these patients may rely on innate defenses that are reconstituted more rapidly than the adaptive ones. In this context, ILCs may represent important players in the early phases following transplantation. They may contribute to tissue homeostasis/remodeling and lymphoid tissue reconstitution. While the reconstitution of NK cell repertoire and its role in haplo-HSCT have been largely investigated, little information is available on ILCs. Of note, CD34+ cells isolated from different sources of HSC may differentiate in vitro toward various ILC subsets. Moreover, cytokines released from leukemia blasts (e.g., IL-1β) may alter the proportions of NK cells and ILC3, suggesting the possibility that leukemia may skew the ILC repertoire. Further studies are required to define the timing of ILC development and their potential protective role after HSCT
Author Correction: Africa needs context-relevant evidence to shape its clean energy future
No full textEFFECTS OF BETA-ENDORPHIN AND D-ALANINE2 ENKEPHALINAMIDE ON URINE PRODUCTION AND URINARY ELECTROLYTES IN THE RAT
No full textThe intracerebro-ventricular administration of human .beta.-Endorphin (.beta.-EP, 0.1-3 .mu.g/rat) or D-alanine2 methionine enkephalinamide (D-ala, 0.3-30 .mu.g/rat) caused a dose dependent reduction in urine volume. The oliguria was associated with a decrease in the concentration of Na+ and K+ in the urine of rats previously hydrated by oral administration with 25 ml/kg tap water plus 50 ml/kg 0.5% NaCl. On a molar basis, .beta.-EP proved to be about 5-7 times more potent than D-ala. The effects caused by the peptides were antagonized by simultaneous i.p. administration of 1 mg/kg naloxone. In rats treated chronically with morphine, no cross-tolerance was demonstrated to the antidiuretic effect of .beta.-EP, but clear cross-tolerance was evident to the changes in urine electrolytes induced by .beta.-EP. Morphine and the opiate peptides may share a similar mechanism of action
Endocrine response and ovum transport in women treated with D-Trp6-luteinizing hormone-releasing hormone in the postovulatory period
No full textPossible alterations in ovum transport during increased activity of the hypothalamic-pituitary-ovarian axis were investigated in women. D-Trp6-luteinizing hormone (LH)-releasing hormone, a synthetic peptide with potent gonadotropin-releasing activity, was used to induce a gonadotropin surge and stimulate ovarian steroid secretion in the postovulatory phase. The compound was administered intramuscularly or intravenously 24, 48, or 72 hours following the maximum preovulatory LH level in plasma in seven women. An immediate and pronounced gonadotropin surge accompanied by a moderate increase in the estradiol and progesterone level was obtained in all cases. Ova were recovered from the fallopian tubes in four of the seven women 24 hours following treatment. The rate of recovery and the location of ova within the genital tract indicate that the treatment and the resulting endocrine changes failed to accelerate migration of the ova toward the uterus. This observation, taken together with oth
Author Correction: Africa needs context-relevant evidence to shape its clean energy future
No full textCorrection to: Nature Energyhttps://doi.org/10.1038/s41560-022-01152-0, published online 24 October 2022 In the version of the article initially published, Gebrekidan Gebresilassie Eshetu’s name appeared incorrectly as Eshetu Gebrekidan Gebresilassie and has now been corrected in the HTML and PDF versions of the article.Water Resource
Group 3 innate lymphoid cells regulate neutrophil migration and function in human decidua
No full textInnate lymphoid cells (ILCs) have a central role in innate defenses against pathogens, lymphoid organogenesis, and tissue remodeling. They have been detected in human decidua, however, their role in this tissue remains unclear. Successful pregnancy requires an early inflammatory phase favoring implantation and tissue remodeling as well as a subsequent regulatory phase to prevent fetal rejection and supporting neoangiogenesis. Here, we show that, during the first trimester of pregnancy, neutrophils infiltrate decidua basalis and are more abundant in normal pregnancy than in spontaneous miscarriages. Decidual neutrophils localize in proximity of NCR(+)ILC3, which may influence neutrophil migration and survival given their production of CXCL8 and granulocyte macrophage colony-stimulating factor (GM-CSF). Moreover, NCR(+)ILC3-derived GM-CSF was found to induce the expression of heparin-binding EGF-like growth factor and IL1ra in neutrophils, two proteins/cytokines involved in tissue remodeling and maintenance of pregnancy. Our data suggest that the simultaneous presence of NCR(+)ILC3 and neutrophils in decidual tissues and their possible cross talk, may have a role in the early phases of pregnancy.Mucosal Immunology advance online publication, 24 February 2016; doi:10.1038/mi.2016.10
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