Natural Killer Cytotoxicity In Patients Research Articles

Natural killer cell cytotoxicity in patients with recurrent herpes infections: diagnostic utility of a flow cytometric assay

BackgroundPrimary immune deficiencies of natural killer (NK) cells have been described in patients with a susceptibility to herpes infections.AimsTo assess the diagnostic utility of measurement of NK cytotoxicity in patients...

Interleukin-15 Upregulates the Expression of NK-Cell Activating Receptors and Concomitantly Increases the NK Cytotoxicity in Patients with Acute Myeloid Leukemia.

Natural killer (NK) cells lyse malignant cells without prior antigen-specific priming and play a critical role in the innate immune response. A balance of signals from activating and inhibiting receptors expressed on each NK cell controls its activity. The growth, differentiation and survival of NK cells have been found to be dependent on interleukin-15 (IL-15). Using multicolor flow cytometry we investigated the receptor repertoire and also measured the NK cell activity in twenty three patients with newly diagnosed acute myeloid leukemia (AML) prior to any treatment. Further, we investigated the ex-vivo effect of IL-15 on the NK cell repertoire and NK cell cytotoxicity. The percentage of circulating NK cells was lower (p<0.0001) in the AML patients (6%± 0.7, range 1–17%) compared to the NK cells of healthy donors (12%± 1, range 9–17%). The expression of the activating natural cytotoxicity (NCR) receptors NKp30 and NKp46 and the C-type lectin receptors NKG2D and NKG2C was significantly decreased in the AML patients compared to the NK cells of healthy donors: NKp30 24 vs 51% p<0.0001, NKp46 32 vs 73% p<0.0001, NKG2D 43 vs 83% p<0.0001, NKG2C 17 vs 28% p<0.03. In addition, the receptor expression (mean fluorescence intensity, MFI) was also significantly lower in AML patients compared to healthy donors. No significant differences in the expression of the NCR NKp44 and the NK- cell inhibitory receptors were observed. Furthermore, the NK cytotoxicity in the AML patients at diagnosis was significantly lower (p<0.0003) compared to the NK cytotoxicity of healthy donors (4 vs 75 LU). When NK cells obtained from AML patients were cultured with IL-15, significant increases in the expression of the NK- cell activating receptors (Table 1) were observed. The upregulation of the activating receptors was associated with a concomitant significant increase (p<0.001) of the NK cell cytotoxicity (4 vs 70 LU). The data suggest that IL-15, a homeostatic NK cell cytokine, can upregulate the expression of activating receptors and concomitantly increase the NK lytic activity. The use of IL-15 as a platform for NK- based therapies for AML patients should be considered in the future.Table 1The effect of IL-15 on the receptor expression in AML patientsNK cell Activating ReceptorsNK cells in AML pts at diagnosisNK cells in AML pts after IL-15 stimulationp value% positive, MFI% positive, MFINKp3024, 2.684, 6.00.001NKp444, 2.471, 6.70.001NKp4632, 2.683, 70.002NKG2C17, 2.258, 6.90.005NKG2D43, 2.587, 7.80.01

Spontaneous and Cytokine-Induced Natural Killer Cytotoxicity in Patients With Cushing???s Disease

Fil: Cardoso, Estela M. del Lujan. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Investigaciones Medicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Medicas; Argentina

Clinical Implications of Natural Killer Cytotoxicity in Patients with Squamous Cell Carcinoma of the Penis

Impairment of natural cytotoxicity mediated by natural killer (NK) cells may play a role in the pathogenesis of penile carcinoma. The aim of this study was to examine the NK activity profile and its prognostic significance in patients with squamous cell carcinoma of the penis. The NK activity was measured in peripheral blood mononuclear cells (PBMCs) from 39 patients diagnosed histologically as having invasive squamous cell penile carcinoma and 4 patients with verrucous carcinoma of the penis. Of 39 patients with invasive squamous cell carcinoma, 4 had undergone previous penile amputation. According to the prognosis, the patients with invasive squamous cell carcinoma were divided into two groups: with metastasis and without metastasis. The patients were evaluated in relation to clinicopathologic variables using univariate analyses. NK cell activity was significantly decreased in all patients with penile carcinoma when compared with the control groups (p < 0.0001). There was no statistically significant difference between the groups with and without metastasis. We conclude that there is a decrease in NK activity in PBMCs from patients with penile carcinoma and that the presence of advanced disease or metastatic involvement is not responsible for this reduction.

Transfusion History, T Cell Subsets and Natural Killer Cytotoxicity in Patients with Colorectal Cancer1

Blood transfusions are associated with clinical phenomena which are attributable to immune suppression. Since suppression of immune function is associated with a high risk of spontaneous malignancies, we studied T cell subsets and natural killer (NK) cytotoxicity in colorectal cancer patients and correlated the results with patients' transfusion histories. Twelve percent (14) of the 115 patients had been transfused an average of 19 years previously. Recipients of blood transfusions had low levels of peripheral lymphocytes (p = 0.191), T cells (p = 0.015), helper cells (p = 0.016) and suppressor cells (p = 0.2651) compared to previously untransfused patients. NK cytotoxicity was also significantly reduced in transfusion recipients although NK cell numbers were comparable in both groups. These results support previous studies indicating that blood transfusions cause lifelong immune modulation in the recipient. Since blood transfusions have numerous beneficial effects and immune modulation is often beneficial, longitudinal studies are necessary to define the lifetime risks and benefits.

Transfusion History, T Cell Subsets and Natural Killer Cytotoxicity in Patients with Colorectal Cancer

Blood transfusions are associated with clinical phenomena which are attributable to immune suppression. Since suppression of immune function is associated with a high risk of spontaneous malignancies, we studied T cell subsets and natural killer (NK) cytotoxicity in colorectal cancer patients and correlated the results with patients’ transfusion histories. Twelve percent (14) of the 115 patients had been transfused an average of 19 years previously. Recipients of blood transfusions had low levels of peripheral lymphocytes (p=0.191 ), T cells (p=0.015), helper cells (p=0.016) and suppressor cells (p=0.2651) compared to previously untransfused patients. NK cytotoxicity was also significantly reduced in transfusion recipients although NK cell numbers were comparable in both groups. These results support previous studies indicating that blood transfusions cause lifelong immune modulation in the recipient. Since blood transfusions have numerous beneficial effects and immune modulation is often beneficial, longitudinal studies are necessary to define the lifetime risks and benefits.

The prognostic significance of natural killer cytotoxicity in patients with colorectal cancer.

We evaluate the prognostic significance of preoperative natural killer (NK) cytotoxicity for K562 cells and its relationship to other prognostic factors in 102 patients with colorectal cancer who underwent curative resections between February 1984 and February 1985. The 18 patients who had recurrences within two years of surgery had significantly higher numbers of preoperative peripheral blood suppressor/cytotoxic and NK cells and significantly lower preoperative NK cytotoxicity than disease-free patients. Low preoperative NK cytotoxicity was predictive of recurrence independent of age, sex, hematocrit, procedure, blood loss, duration of surgery, Dukes' stage, specimen length, tumor size, tumor differentiation, and post-operative therapy. Low levels of in vitro NK-cell cytotoxicity may identify a subgroup of patients at high risk for recurrence.

Effect of lymphokines on natural killer cytotoxicity in patients with high risk of developing the acquired immune deficiency syndrome

Regulation of natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) from patients with the acquired immune deficiency syndrome (AIDS) and from individuals at high risk of developing AIDS (R-AIDS) was studied. The response of untreated PBMC to the interferon inducer polyinosinic polycytidilic acid (Poly I:C) was lower in AIDS and R-AIDS than in normal controls and PBMC from R-AIDS were more susceptible to stimulation with lymphokine rich supernatants (Con-A-SN, PHA-SN, lectin free IL-2) than AIDS and normal controls. To determine the role of the different T lymphocyte subsets in the regulation of NK activity, PBMC were selectively treated with monoclonal non-cytotoxic anti-Leu 2a and anti-Leu 3a anti-bodies and then stimulated with lymphokine rich supernatants. The results indicate that the effect of crude supernatants was the combination of opposite effects. Leu 2a-blocked R-AIDS-PBMC enhanced NK cytotoxicity when exposed to IL-2 rich supernatants whereas Leu 3a-blocked R-AIDS-PBMC suppressed the cytotoxic reaction.

The nature of enhanced natural killer lymphocyte cytotoxicity during anesthesia and surgery in patients with benign disease and cancer.

This study was instituted to determine the mechanism of enhanced natural killer (NK) lymphocyte activity during surgery. Natural cytotoxicity of whole blood to K562 target cells was assayed before anesthesia and during anesthesia and surgery in patients with benign and malignant gastrointestinal disease. Those patients with benign conditions and localized primary tumors showed enhanced NK lymphocyte cytotoxicity during surgery (p less than 0.025 and p less than 0.0025, respectively) but not patients with disseminated tumors. In patients with localized tumors, enhancement of NK lymphocyte cytotoxicity was an interferon-independent phenomenon but appeared to be related to a significant rise in the percentage of cells bearing the Leu 7 monoclonal antibody marker for NK cells (p less than 0.02). Exogenous leukocyte interferon caused further enhancement of NK cytotoxicity in patients with benign disease and some cancer patients. Enhancement of NK lymphocyte activity during surgery may be of significance in reducing tumor metastases by stimulation of natural cytotoxic mechanisms to circulating tumor emboli.