Functional Characterictics of Bone Marrow Immune Suppressive Cells in Patients with Gastric Cancer

1998 ◽  
Vol 11 (3) ◽  
pp. 171-178 ◽  
Author(s):  
S. A. Kusmartsev ◽  
I. N. Kusmartseva ◽  
N.V. Tcherdyntseva ◽  
S.G. Afanasyev ◽  
N.V. Vasilyev
Keyword(s):  
Gastric Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Activity ◽  
Adherent Cell ◽  
Target Cells ◽  
Suppressive Activity ◽  
Normal Peripheral Blood

The progressive growth of cancer is accompanied by alteration in the regulation of both hematopoiesis and immunity. In this study we assessed the immunoregulatory features of bone marrow (BM) plastic non-adherent cells in patients with primary gastric cancer. Suppressive activity of BM cells or its culture supernatants was determined by inhibition of normal peripheral blood mononuclear cells (PBMC) response to phytohemagglutinin (PHA) or NK cell cytotoxicity. It was shown that fresh isolated BM cells from gastric cancer patients are capable markedly inhibit the mitogen-induced proliferative response of PBMC as well as NK cell cytotoxic activity. The immune suppressive cell activity was revealed among the non-adherent cell fraction only. The addition of indomethacin, inhibitor of prostaglandin synthesis, or NG-monomethyl-L-arginine (L-NMA), a competitive inhibitor of nitric oxide (NO) synthase, to the cultures did not diminish the suppressive effect of non-adherent BM cells in cancer patients. This BM cell mediated suppression of mitogen-induced proliferation of PBMC could be reduced, at least in part, by addition of neutralizing monoclonal antibodies to TGF-β. When normal PBMC were cultured with supernatant of BM cells derived from cancer patients, their natural killer cell activity was strongly down-regulated. It was shown also that NK cell capacity to bind tumor target cells was reduced in the presence of BM cell supernatant. Taken together our data demonstrate that BM non-adherent cell of patients with gastric cancer exhibit the immune suppressive activity which should be supposed to contribute to impairment of tumor immunity as malignant growth progresses.

scholarly journals Patients with a deficiency of natural killer cell activity lack the VEP13-positive lymphocyte subpopulation

Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 65-70 ◽  
Author(s):  
HW Ziegler-Heitbrock ◽  
H Rumpold ◽  
D Kraft ◽  
C Wagenpfeil ◽  
R Munker ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Target Cells ◽  
Nk Cell Activity

Many patients with B-type chronic lymphocytic leukemia (CLL) exhibit a profound defect in their natural killer (NK) cell activity, the basis of which is still obscure. Hence, we analyzed the NK cells from peripheral blood samples from 11 patients with CLL for phenotype and function, after removal of the leukemic cells with a monoclonal antibody (BA-1) plus complement. Phenotypic analysis of these nonleukemic cells with monoclonal antibodies (MoAbs) against NK cells revealed that the CLL patients had higher percentages of HNK-1-positive cells (23.5% compared to controls with 14.7%). In contrast, VEP13- positive cells were absent or low in seven patients (0.8% compared to controls with 11.2%) and normal in four patients (10.5%). When testing NK cell activities against K562 or MOLT 4 target cells, patients with no or minimal numbers of VEP13-positive cells were found to be deficient, while patients with normal percentages of VEP13-positive cells had NK cell activity comparable to controls. Isolation by fluorescence-activated cell sorter of HNK-1-positive cells from patients lacking VEP13-positive cells and NK cell activity indicated that the majority of the HNK-1-positive cells in these patients had the large granular lymphocyte morphology that is characteristic of NK cells. Thus, the deficiency of NK cell activity in CLL patients appears to result from the absence of cells carrying the VEP13 marker.

Effect of Conventional Chemotherapies on Natural Killer Cell Activity

2021 ◽  
Vol 17 ◽  
Author(s):  
Idris Kirhan ◽  
Huseyin Taskiran ◽  
Ataman Gönel
Keyword(s):  
Immune System ◽  
Natural Killer ◽  
Cancer Patients ◽  
Nk Cell ◽  
Metastatic Cancer ◽  
Critical Role ◽  
Killer Cell ◽  
Cell Activity ◽  
Activity Levels ◽  
Nk Cell Activity

Background: The effects of chemotherapeutics agents are considered to influence immune system and cells due to their myelosuppressive and immunosuppressive functions. Natural Killer Cells are one of the important components of innate immune system and have a critical role against tumor cells and infections. Objective: The study was aimed to demonstrate whether conventional chemotherapies had an effect on Natural Killer (NK) cell activity. Methods: 49 adjuvant, 19 first time metastatic chemotherapy-naïve cancer patients were recruited into the study. Pre-chemotherapy and post-chemotherapy, at 1th and 4th cycles, blood samples were obtained for NK cell activity. Results: We found no difference between baseline and post-chemotherapy NK cell activity levels. In addition, we found no difference between pre-chemotherapy and post-chemotherapy NK cell activity in both adjuvant and metastatic cancer patients separately. Conclusion: Conventional chemotherapy seems to no affect NK cell activity levels in cancer patients in both metastatic and adjuvant settings.

Effects of Emitted Qi on In Vitro Natural Killer Cell Cytotoxic Activity

2001 ◽  
Vol 29 (01) ◽  
pp. 17-22 ◽  
Author(s):  
Myeong Soo Lee ◽  
Hwa Jeong Huh ◽  
Hye-Sook Jang ◽  
Chang Sub Han ◽  
Hoon Ryu ◽  
...  
Keyword(s):  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Activity ◽  
K562 Cells ◽  
Target Cells ◽  
Cell Cytotoxicity ◽  
Nk Cell Activity ◽  
Nk Cell Cytotoxicity

The present study investigated the effects of Korean Qi-therapy, ChunSoo Energy Healing, on natural killer (NK) cell cytotoxicity in vitro depending on Qi-treatment time and the types of cells treated. NK cell cytotoxicity was assayed by measuring LDH release from tumor target cells (K562 cell lines). NK activity was significantly increased by emitted-Qi treatment of 30 sec duration. Three and 5 minutes of Qi projection created the greatest increase in NK cell activity when mixtures of NK cells and K562 cells were treated (1.81 and 2.12 fold for 4 hr culture; 1.54 and 1.36 for 16 hr culture, respectively). NK cell activity increased significantly in Qi-treated K562 cells alone (1.13 fold, p < 0.05) compared to control. These results are consistent with in vivo Qi-therapy on humans and suggests that emitted-Qi has an acute stimulatory effect on NK cell activity. This study provides direct scientific support that Qi as such may positively affect human cellular immunity.

scholarly journals Differential natural killer cell–mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes

2007 ◽  
Vol 204 (12) ◽  
pp. 3027-3036 ◽  
Author(s):  
Galit Alter ◽  
Maureen P. Martin ◽  
Nickolas Teigen ◽  
William H. Carr ◽  
Todd J. Suscovich ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Activity ◽  
Cell Contact ◽  
Target Cells ◽  
Dependent Manner ◽  
Hiv 1

Decline of peak viremia during acute HIV-1 infection occurs before the development of vigorous adaptive immunity, and the level of decline correlates inversely with the rate of AIDS progression, implicating a potential role for the innate immune response in determining disease outcome. The combined expression of an activating natural killer (NK) cell receptor, the killer immunoglobulin-like receptor (KIR) 3DS1, and its presumed ligand, human leukocyte antigen (HLA)–B Bw4-80I, has been associated in epidemiological studies with a slow progression to AIDS. We examined the functional ability of NK cells to differentially control HIV-1 replication in vitro based on their KIR and HLA types. NK cells expressing KIR3DS1 showed strong, significant dose- and cell contact–dependent inhibition of HIV-1 replication in target cells expressing HLA-B Bw4-80I compared with NK cells that did not express KIR3DS1. Furthermore, KIR3DS1+ NK cells and NKLs were preferentially activated, and lysed HIV-1 infected target cells in an HLA-B Bw4-80I–dependent manner. These data provide the first functional evidence that variation at the KIR locus influences the effectiveness of NK cell activity in the containment of viral replication.

scholarly journals Differential Cytotoxicity of Cord Blood and Bone Marrow–Derived Natural Killer Cells

Blood ◽  
1998 ◽  
Vol 91 (1) ◽  
pp. 207-213
Author(s):  
Clair M. Gardiner ◽  
Anne O' Meara ◽  
Denis J. Reen
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Cytotoxic Activity ◽  
Natural Killer ◽  
Nk Cell ◽  
Granzyme B ◽  
Cell Activity ◽  
Lak Cells ◽  
Target Cells ◽  
Nk Cell Activity

Allogeneic cord blood is now being widely used as a source of stem cells for hematologic reconstitution after myeloablative therapy, with reported significantly lower levels of graft-versus-host disease (GVHD) compared with the use of allogeneic bone marrow (BM). This study was undertaken to investigate biologic aspects of natural killer (NK) cell activity, as recognized effector cells of the GVHD and graft-versus-leukemia (GVL) response, from cord blood and conventional BM. NK-cell activity levels of freshly isolated cells from cord blood and BM against K562 targets were comparable. Lymphokine activated killer (LAK) cells from both hematopoietic cell sources were compared for their ability to kill target cells by necrotic or apoptotic mechanisms using specific target cell lines. Cord blood cells had significantly higher necrosis-mediated cytotoxic activity against Daudi target cells compared with BM-derived cells. Cord blood LAK cells had relatively high levels of apoptotic-mediated cytotoxicity against YAC-1 target cells, whereas BM-derived LAK cells were unable to induce apoptosis in these cells. Interleukin-2 (IL-2) induced significant granzyme B activity in cord cells in contrast to BM cells, in which very little activity was measured. Western blotting confirmed these findings, with IL-2 inducing granzyme B protein expression in cord cells but not detectable levels in BM cells. BM cells had significantly lower cell surface expression of IL-2R and prolonged culture in IL-2 was only partially able to restore their deficient apoptotic cytotoxic activity. Thus, major differences exist between cord blood-derived and BM-derived mononuclear cells with respect to their NK-cell–associated cytotoxic behavior. This could have important implications for stem cell transplantation phenomena, because it suggests that cord blood may have increased potential for a GVL effect.

scholarly journals Identification of Primary Natural Killer Cell Modulators by Chemical Library Screening with a Luciferase-Based Functional Assay

2018 ◽  
Vol 24 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Simon Hayek ◽  
Nassima Bekaddour ◽  
Laurie Besson ◽  
Rodolphe Alves de Sousa ◽  
Nicolas Pietrancosta ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Activity ◽  
Target Cells ◽  
Functional Assay ◽  
Functional Screening ◽  
Cell Functions ◽  
Ifn Γ

Natural killer (NK) cells are essential players of the innate immune response that secrete cytolytic factors and cytokines such as IFN-γ when contacting virus-infected or tumor cells. They represent prime targets in immunotherapy as defects in NK cell functions are hallmarks of many pathological conditions, such as cancer and chronic infections. The functional screening of chemical libraries or biologics would greatly help identify new modulators of NK cell activity, but commonly used methods such as flow cytometry are not easily scalable to high-throughput settings. Here we describe an efficient assay to measure the natural cytotoxicity of primary NK cells where the bioluminescent enzyme NanoLuc is constitutively expressed in the cytoplasm of target cells and is released in co-culture supernatants when lysis occurs. We fully characterized this assay using either purified NK cells or total peripheral blood mononuclear cells (PBMCs), including some patient samples, as effector cells. A pilot screen was also performed on a library of 782 metabolites, xenobiotics, and common drugs, which identified dextrometorphan and diphenhydramine as novel NK cell inhibitors. Finally, this assay was further improved by developing a dual-reporter cell line to simultaneously measure NK cell cytotoxicity and IFN-γ secretion in a single well, extending the potential of this system.

scholarly journals Differential Cytotoxicity of Cord Blood and Bone Marrow–Derived Natural Killer Cells

Blood ◽  
1998 ◽  
Vol 91 (1) ◽  
pp. 207-213 ◽  
Author(s):  
Clair M. Gardiner ◽  
Anne O' Meara ◽  
Denis J. Reen
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Cytotoxic Activity ◽  
Natural Killer ◽  
Nk Cell ◽  
Granzyme B ◽  
Cell Activity ◽  
Lak Cells ◽  
Target Cells ◽  
Nk Cell Activity

Abstract Allogeneic cord blood is now being widely used as a source of stem cells for hematologic reconstitution after myeloablative therapy, with reported significantly lower levels of graft-versus-host disease (GVHD) compared with the use of allogeneic bone marrow (BM). This study was undertaken to investigate biologic aspects of natural killer (NK) cell activity, as recognized effector cells of the GVHD and graft-versus-leukemia (GVL) response, from cord blood and conventional BM. NK-cell activity levels of freshly isolated cells from cord blood and BM against K562 targets were comparable. Lymphokine activated killer (LAK) cells from both hematopoietic cell sources were compared for their ability to kill target cells by necrotic or apoptotic mechanisms using specific target cell lines. Cord blood cells had significantly higher necrosis-mediated cytotoxic activity against Daudi target cells compared with BM-derived cells. Cord blood LAK cells had relatively high levels of apoptotic-mediated cytotoxicity against YAC-1 target cells, whereas BM-derived LAK cells were unable to induce apoptosis in these cells. Interleukin-2 (IL-2) induced significant granzyme B activity in cord cells in contrast to BM cells, in which very little activity was measured. Western blotting confirmed these findings, with IL-2 inducing granzyme B protein expression in cord cells but not detectable levels in BM cells. BM cells had significantly lower cell surface expression of IL-2R and prolonged culture in IL-2 was only partially able to restore their deficient apoptotic cytotoxic activity. Thus, major differences exist between cord blood-derived and BM-derived mononuclear cells with respect to their NK-cell–associated cytotoxic behavior. This could have important implications for stem cell transplantation phenomena, because it suggests that cord blood may have increased potential for a GVL effect.

scholarly journals The role of cytokine in regulation of the natural killer cell activity

2008 ◽  
Vol 136 (7-8) ◽  
pp. 423-429 ◽  
Author(s):  
Vladimir Jurisic ◽  
Sladjana Stojacic-Djenic ◽  
Natasa Colovic ◽  
Gordana Konjevic
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Function ◽  
Nk Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Target Cells

Natural killer (NK) cells are characterized by a CD3-CD16+ CD56+ immunophenotype and have a central role in the innate immune system. They are defined by their capacity to kill certain tumor-target cells or virus infected cells without prior sensitization or MHC-restriction. The activity of the NK cells is determined by the balance between activation and inhibitory receptor molecules expressed on the surface of NK cells. However, several cytokines and chemokines can significantly modulate their activity, inducing increase of NK cell activity. Immunomodulation mediated by NK cells is very important mechanism in tumor immunity, as well as in other immunodepressions of the immune system. In this study, we summarize the role of several cytokines, including IFN, IL-1, IL-2, IL-4, IL-7, IL-12 and IL-17, on NK cell function. The NK cells, after activation, depending on cytokine environment, can differentiate into NK1 cells that produce Th1 cytokine type (IFN-?, IL-2, IL-12) or NK2 cells that produce Th2 type cytokines, enhance exocytosis and release of previously formed molecules from NK cells (granzyme, perforin). We also describe that the release of cytokines and mediators show local or distance effects, or induce apoptosis (mostly by secreted TNF-?) after binding appropriated killer cell receptors from TNF receptor superfamily.

Natural Killer Cell Activity in Rainbow Trout (Salmo gairdneri): Effect of Dietary Exposure to Aroclor 1254 and/or Mirex

1987 ◽  
Vol 44 (3) ◽  
pp. 636-638 ◽  
Author(s):  
Glenn B. Cleland ◽  
Ronald A. Sonstegard
Keyword(s):  
Rainbow Trout ◽  
Natural Killer ◽  
Nk Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Dietary Exposure ◽  
Salmo Gairdneri ◽  
Target Cells ◽  
Aroclor 1254

Rainbow trout (Salmo gairdneri) peripheral blood lymphocytes and splenocytes were found to have spontaneous cytotoxic activity against cultured mammalian and fish tumor cell lines. P 815 and YAC 1 target cells were found to be highly sensitive to trout natural killer (NK) cell lysis, while K 562 and ML cells were low and EL 4 was resistant. NK cell activity was not significantly altered by a 12-mo dietary exposure of fish to various concentrations of Aroclor 1254 and/or mirex.

Sign in / Sign up

Export Citation Format

Share Document