Regulation of human natural cytotoxicity by IgG—I. Characterization of the structural site on monomeric IgG responsible for inhibiting natural killer cell activity

Gherman, M; Manciulea, Mioara; Bancu, Alexandru; Sulica, Andrei; Stanworth, D.R.; Herberman, Ronald B.

doi:10.1016/0161-5890(87)90057-5

Cited by 20 publications

(11 citation statements)

References 31 publications

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“…These studies have shown differing results. Thus, whereas for some groups the PB spontaneous NK-cell activity is decreased in MM patients (Komiyama et al, 1986;Gherman et al, 1987;Ogmunsdottir, 1988;Ö sterborg et al, 1990), others failed to reproduce these findings (Nielsen et al, 1991;Facon et al, 1993). Regarding the NK activity of BM cells, Uchida et al (1984) reported an increased NK-activity in the BM of MM patients; however, this strong activity was found against the K562 cells but not against autologous myeloma cells (Bianchi et al, 1990;Hoover & Kornbluth, 1992).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have focused on either the B lymphocytes, which might belong to the tumoural clone (Pilarski & Jensen, 1992), or the T-cell subsets (San Miguel et al, 1991), and have shown that both lymphoid populations may play an important role in the course of the disease in myeloma patients. Recently, attention has also been paid to other accessory cells such as NK cells (Uchida et al, 1984;Komiyama et al, 1986;Gherman et al, 1987;Kimata et al, 1987;Shimazaki et al, 1988;Ogsmundottir, 1988;Hoover & Kornbluth, 1992;Facon et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…Most of the studies dealing with NK cells in multiple myeloma have focused on the analysis of their lytic capacity against target cells (Uchida et al, 1986;Komiyama et al, 1986;Gherman et al, 1987;Kimata et al, 1987;Shimazaki et al, 1988;Ogsmundottir, 1988;Nielsen et al, 1991;Hoover & Kornbluth, 1992). These studies have shown differing results.…”

Section: Discussionmentioning

confidence: 99%

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Analysis of natural killer‐associated antigens in peripheral blood and bone marrow of multiple myeloma patients and prognostic implications

et al. 1996

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The aim of this study was to analyse the expression of NK-associated antigens in both peripheral blood and bone marrow lymphocytes from a large series of newly diagnosed multiple myeloma patients. 112 patients with untreated multiple myeloma (MM) were included in the study. 36 sex- and age-matched healthy volunteers were used as controls for peripheral blood (PB) studies and 14 for the bone marrow (BM) studies. Simultaneous stainings with the CD3/CD56, CD2/CD16 and CD8/CD57 monoclonal antibodies were systematically performed in PB and CD3/CD56 and CD2/CD16 in BM in order to analyse their relationship with the clinical and biological characteristics of the disease and survival. The expression of NK-associated antigens (CD56, CD16 and CD57) assessed within the lymphoid gate, was significantly increased (P < 0.001) in the PB of MM patients both in relative and absolute numbers. In the BM a significant increase in the percentage of CD56+ lymphocytes (P < 0.001) was also observed; in contrast, the proportion of CD16+ cells did not differ significantly from that of normal BM samples. The number of CD56+CD3- lymphocytes increased significantly within high-risk patients (869 +/- 671) as compared to intermediate (388 +/- 212) and low-risk patients (274 +/- 199) (P = 0.04). Moreover, patients with high values of CD56+CD3- lymphocytes showed a statistically significant association with several adverse prognostic factors including anaemia, hypoalbuminaemia, renal failure, high beta 2M, DNA diploidy and high S-phase plasma cells. In addition, patients with higher absolute numbers of PB CD56+CD3-lymphocytes displayed a poorer prognosis, whereas patients with higher values of CD57+CD8- cells had a better outcome.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Analysis of natural killer‐associated antigens in peripheral blood and bone marrow of multiple myeloma patients and prognostic implications

et al. 1996

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“…Unfortunately, autologous NK cells from patients with MM appear to be dysfunctional. These NK cells can have an unfavourable balance between activating and inhibitory receptors (Fauriat et al, 2006;Costello et al, 2013) and can be inhibited by the products of plasma cells (Gherman et al, 1987) and the hypoxic bone marrow microenvironment itself (Sarkar et al, 2013). Furthermore possible protection by class I expression (Carbone et al, 2005;Gao et al, 2014) in some patients suggests that any successful activity against MM requires highly active NK cells, ideally from an allogeneic source.…”

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confidence: 99%

Phase I study of cord blood-derived natural killer cells combined with autologous stem cell transplantation in multiple myeloma

et al. 2017

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Summary Multiple myeloma (MM) is a disease with known immune dysregulation. Natural killer (NK) cells have shown preclinical activity in MM. We conducted a first-in-human study of umbilical cord blood-derived (CB) NK cells for MM patients undergoing high dose chemotherapy and autologous haematopoietic stem cell transplantation (auto-HCT). Patients received lenalidomide (10 mg) on days −8 to −2, melphalan 200 mg/m2 on day −7, CB-NK cells on day −5 and auto-HCT on day 0. Twelve patients were enrolled, 3 on each of four CB-NK cell dose levels: 5×106, 1×107, 5×107 and 1×108 CB-NK cells/kg. Ten patients had either high-risk chromosomal changes or a history of relapsed/progressed disease. There were no infusional toxicities and no graft-versus-host disease. One patient failed to engraft due to poor autologous graft quality and was rescued with a back-up autologous graft. Overall, 10 patients achieved at least a very good partial response as their best response, including 8 with near complete response or better. With a median follow-up of 21 months, 4 patients have progressed or relapsed, 2 of whom have died. CB-NK cells were detected in vivo in 6 patients, with an activated phenotype (NKG2D+/NKp30+). These data warrant further development of this novel cellular therapy.

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“…2. Induced by Fc fragments of IgG, either polyclonal or monoclonal, as well as by the synthetic peptide Tyr407-Arg416 localized in the CH3 domain[61].3. Results from direct interaclion of cytophilic IgG molecules with FcyRIlIa onhuman NK cells[67].…”

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confidence: 99%

Ig-binding Receptors on Human NK Cells as Effector and Regulatory Surface Molecules

Sulica¹,

Morel

Metes

et al. 2001

International Reviews of Immunology

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The receptors on human natural killer 9NK cells which can specifically bind the Fc portion of immunoglobulin molecules (Fc receptors) have been extensively studied. The best known and studied Fc receptor on human NK cells is FcgammaRIIIa. Interactions of NK cells with IgG antibodies via this receptor are well known to induce a signal transduction cascade and lead to antibody-dependent cell-mediated cytotoxicity (ADCC) as well as release of various cytokines. In addition, interactions with monomeric IgG and FcgammaRIIIa have been demonstrated, which result in negative regulation of NK activity and other immunomodulatory effects. Over the past several years, it has also become increasingly appreciated that human NK cells express a variety of other Fc receptors, including FcmuR, which also can mediate effector and immunoregulatory functions. Also, a novel form of FcgammaR has been demonstrated on human NK cells, termed FcgammaRIIc. Recent molecular studies have shown considerable polymorphism in the genes for FcgammaIIc and the functional consequences are being dissected. This appears to include cross-talk between FcgammaRIIIa and at least some forms of FcgammaRIIc, which may have important functional consequences.

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Regulation of human natural cytotoxicity by IgG—I. Characterization of the structural site on monomeric IgG responsible for inhibiting natural killer cell activity

Cited by 20 publications

References 31 publications

Analysis of natural killer‐associated antigens in peripheral blood and bone marrow of multiple myeloma patients and prognostic implications

Analysis of natural killer‐associated antigens in peripheral blood and bone marrow of multiple myeloma patients and prognostic implications

Phase I study of cord blood-derived natural killer cells combined with autologous stem cell transplantation in multiple myeloma

Ig-binding Receptors on Human NK Cells as Effector and Regulatory Surface Molecules

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