Killer Cell Activity In Patients Research Articles

Natural killer cell activity in patients with metastatic castration-resistant prostate cancer treated with enzalutamide.

255 Background: Metastatic castration resistant prostate cancer (mCRPC) is the lethal stage for most patients with prostate cancer (PCa). The need for more reliable prognostic and predictive markers for the management of mCRPC is still unmet. The aim of this study was to elucidate the correlation between Natural Killer cell activity (NKA) and treatment outcome in mCRPC patients. Methods: Blood samples were collected prospectively from 87 patients with mCRPC who were treated by enzalutamide as first line treatment. Samples were collected, in NK Vue tubes, at baseline, and prior to each treatment cycle until treatment change. Tubes were placed in an incubator at 37°C within 15 minutes of sampling. Following 20-24 hours of stimulation the level of interferon-gamma (IFNγ) in the plasma was measured, by ELISA (NK Vue) as a surrogate for NKA. Outcomes data were included as endpoints. Results: At the time of biochemical response, plasma IFNγ decreased significantly compared to levels detected at baseline (z-score= 2.334, p=0.019). Additionally, the level of IFNγ was significantly lower at radiological response compared to values at biochemical progression (z-score=2.168, p=0.030). Regarding outcome data, the whole cohort was divided into four groups. In group 1 (n=41) the IFNγ level remained within a normal range (>250 pg/mL), while in group 2 (n=8) it increased from an abnormal (<250 pg/mL) to a normal level. In group 3 (n=13) it dropped to an abnormal level, and it remained at an abnormal level during treatment in group 4 (n=17). There was a significant difference between patients in group 2 and patients in the other three groups regarding both overall survival, radiological free survival and time to next treatment (HR= 3.98, p= 0.012, HR= 6.10, p=< 0.001 and HR= 6.521, p= < 0.001, compared to group 1 respectively). Conclusions: An inverse correlation between NKA and both treatment response and outcome was observed, suggesting a unique role of NK cells in late stage PCa treated with enzalutamide.

P–386 Uterine Natural Killer Cell function in Recurrent Miscarriage and Implantation Failure: A Systematic Review

Abstract Study question Does uterine natural killer cell functional activity differ in women with recurrent miscarriage (RM) or implantation failure (RIF) compared to fertile controls? Summary answer There is insufficient data to conclusively determine differences in uterine natural killer (NK) cell activity between women with RM/RIF and controls. What is known already Uterine NK cell (uNK) function is central to maintaining healthy pregnancy by promoting placentation and spiral artery vascular remodelling. The range of uNK activity is diverse and includes cytokine secretion, such as IFN-γ, or angiogenic factors which promote vascular remodelling. Despite an abundance of studies investigating peripheral blood NK cell cytotoxicity, there is limited evidence of uNK cytotoxicity. uNK-trophoblast interactions are facilitated by uNK receptors such as CD94, LILRB1 and KIRs. It is possible that dysfunction of these diverse uNK activities plays a more important role in early pregnancy failure than uNK levels. Study design, size, duration We conducted a systematic review of prospective case-control studies investigating uterine natural killer cell activity in patients with RM or RIF versus controls. The aim was to determine whether there was a distinct variation in uNK activity between RM/RIF and controls. We stratified uNK activity into four broad categories: i) regulation and receptors; ii) cytotoxicity; iii) expression of cytokines; iv) effect on uterine vasculature. Participants/materials, setting, methods The electronic database search included MEDLINE, EMBASE, Web of Science and bibliographies from included articles from inception to December 2020 using a combination of MESH and keywords. Search, screen, and data extraction were performed by two reviewers independently. Quality assessment was conducted with ROBINS-I. Out of 4636 studies screened, 30 studies (1696 women) were analysed for uNK activity. Main results and the role of chance Different methods were used to measure uNK activity including immunohistochemistry, flow cytometry, ELISA, PCR and Western blot. Samples were obtained from endometrium during mid-luteal phase or decidua following surgery. 14 studies reported on uNK phenotypes associated with regulation and receptors. RM/RIF patients, compared to controls, demonstrated a reduced expression of KIR2DL4, KIR2DL3/L2/S2 and inhibitory receptors (NKG2A); whereas there was a higher expression of the activating receptor (NKp46) and CD161. One study reported correlation between FoxP3+ T-cells and CD56+ NK cells but another reported no similar correlation with CD57+/CD56+ ratio. Two studies investigating dNK cytotoxicity, using chromium release or lactate dehydrogenase release assays, concluded higher dNK cytotoxicity in RM patients. Eight studies reported on cytokine expression. Interestingly, two studies found lower expression of IFN-g, but four studies reported otherwise in RM patients. Two studies found a higher ratio of dNK producing IFN-γ/TNF-α to those producing IL–4. The rest of the studies reported lower expression of IL–1RA, IL–10, TNF-α, Lnc–49A and higher expression of granzyme B, perforin and PRF–1. Finally, six studies reported on effect of uNK on vasculature. Among the findings were negative correlation between CD16+ uNK and endometrial IL–6 and VEGF, as well as higher angiogenin, VEGF and bFGF expression. Limitations, reasons for caution Functional activity investigated amongst studies varied significantly; this heterogeneity precluded meta-analysis of the data. Heterogeneity also prohibited definitive conclusions on uNK function and pregnancy outcome. Studies presented data in a combination of qualitative and quantitative analysis and variation was seen in the criteria for inclusion of RM, RIF and controls. Wider implications of the findings: uNK levels alone may be insufficient to guide management of early pregnancy failure. Clarification of underlying functional activity may guide therapeutic intervention and help develop new treatments. This review highlights the need for a greater understanding of the role of uNK activity in healthy pregnancy and early pregnancy failure. Trial registration number N/A

The clinical usefulness of natural killer cell activity in patients with suspected or diagnosed prostate cancer: an observational cross-sectional study.

PurposeTo investigate the clinical usefulness of natural killer cell activity (NKA) for detection of prostate cancer (PCa) and prediction of Gleason grade.Patients and methodsWe prospectively enrolled 221 patients who underwent transrectal ultrasound-guided prostate biopsy for suspected PCa due to elevated prostate-specific antigen (PSA) >2.5 ng/mL or abnormal findings on digital rectal examination (n=146), or who were diagnosed with PCa (n=75) between 2016 and 2017. The NKA was compared according to PCa and Gleason grade. Correlation analysis was used to evaluate associations among NKA, PCa, and Gleason grade, and expressed using distribution dot plots. The absolute risk and relative risk of PCa, and odds ratios at different cut-off values of NKA were calculated.ResultsOf the total 221 patients, PCa was identified in 135 (61.9%) patients. When patients were divided according to PCa, there was no significant difference in NKA (1,267.6 vs 1,198.9 pg/mL, P=0.491). Furthermore, in 135 patients with PCa, the NKA was not significantly different according to Gleason grade (P=0.893). These results were not changed when confined to the patients with PSA between 2.5 and 10.0 ng/mL (P=0.654 and P=0.672, respectively). In addition, there was no significant difference in the risk of PCa at different cut-off values of NKA.ConclusionThese results indicate that NKA does not appear to be very useful for detection of PCa and prediction of Gleason grade. Further large multi-institutional studies are required to verify the role of NKA in PCa detection and Gleason grade prediction.

Natural killer cell activity in patients with major depressive disorder treated with escitalopram

BackgroundAn association between depression and altered immunity has been suggested by many studies, although the findings are not fully consistent. The present investigation examined the effects of escitalopram on cellular immunity in patients with major depressive disorder (MDD). MethodsFifty-one patients with MDD were evaluated with the Hamilton Rating Scale for Depression and Montgomery–Åsberg Depression Rating Scale. The patients were grouped into responders (n=32) and non-responders (n=19). Adrenocorticotropic hormone, cortisol, CD4, CD8, CD19, and natural killer cells were measured at baseline and after a 4week treatment with escitalopram. Plasma hormones and immune parameters were compared between groups. ResultsResponders showed increased activity, but not number, of natural killer cells after a 4week treatment with escitalopram. There were no differences in plasma hormones and other immune parameters between groups, even though cortisol was decreased and CD19 was increased across both groups compared to baseline. ConclusionsThe results suggest that natural killer cells play an important role in improving the symptoms of depressive patients responding to selective serotonin inhibitors. To deepen our understanding of the pathogenesis of depression, interactions between serotonin and the immune system should be further explored.

26. The study of natural killer cell activity in patients with at-risk mental state and with the first-episode schizophrenia

Several studies have shown a decrease of natural killer cell activity (NKCA) in patients with chronic schizophrenia. However, the role of natural killer cells in the pathogenesis of the disease, as well as the influence of psychotropic therapy on their activity is not well understood. The aim of the current study was to compare the NKCA in male patients with at-risk mental state (n = 19) and with the first-episode schizophrenia (n = 33). The effect of serotonin and psychotropic therapy on NKCA also was observed. Twenty-two healthy sex and age matched donors were examined as a control. The NKCA was expressed as an index of cytotoxicity (IC, %). The greatest decrease of NKCA was noticed in patients with at-risk mental state (IC = 29.6%). Its value was higher (IC = 43.8%) in patients with the first-episode schizophrenia than with at-risk mental state (p < 0.05). Nevertheless NKCA remained below the control (IC = 65.2%, p < 0.001) in both groups of patients. NKCA significantly changed during therapy in patients with the first-episode schizophrenia. These data indicate an involvement of natural killer cells in a response to the antipsychotic treatment. Serotonin added to the cell culture in vitro enhanced NKCA to normal (p < 0.05) only in those patients with the first-episode schizophrenia who responded positively to the treatment. In conclusion, these results suggest that NKCA decreases at a preclinical stage of schizophrenia and changes during psychotropic therapy.

Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor- 1

Natural 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. We investigated the microvesicle protein level, molecular profile and suppression of natural killer cell activity in patients with newly diagnosed acute myeloid leukemia. The 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. We 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.

Lymphocyte Subgroups and Natural Killer Cell Activity in Recurrent Herpetic Stromal Keratitis

Although the role of natural killer cells in the defense against certain viral infections has been published, little is known about the role of lymphocyte subgroups in recurrent herpetic stromal keratitis. Accordingly, serum levels of major immunoglobulins (IgG, IgA, and IgM) and IgG subgroups, the lymphocyte subgroups, and natural killer cell activity were investigated in patients with recurrent herpetic stromal keratitis. Eleven patients with recurrent herpetic stromal keratitis and 10 healthy subjects were included. A delayed-type hypersensitivity skin test was performed in addition to the determination of serum immunoglobulin levels, IgG subgroups, peripheral blood lymphocyte percentages, and natural killer cell activity in both groups. The result of the delayed-type hypersensitivity skin test was positive in all patients with recurrent herpetic stromal keratitis and healthy subjects. No significant difference was obtained in serum immunoglobulin levels and IgG subgroups between the patients and healthy subjects. Among the cell surface antigens (CD3, CD4, CD8, CD16, CD19, and CD20), only CD8+ (i.e., cytotoxic) T-lymphocyte percentages were significantly increased (P=0.003), and the CD4:CD8 ratio was significantly decreased in the patients compared to the healthy subjects (P=0.021). There was no significant difference in the expression of CD16+ natural killer cells between both groups, despite a significantly lower natural killer cell activity in patients with recurrent herpetic stromal keratitis (P=0.011). These results indicate that human cytotoxic T cells show a difference in numbers and natural killer cell activity that may affect the prognosis of recurrent herpetic stromal keratitis.

Time course characteristics of human herpesvirus 6 specific cellular immune response and natural killer cell activity in patients with exanthema subitum

The time-course of cell-mediated immunity in exanthema subitum is not well documented. The lymphoproliferative response to purified human herpesvirus 6 (HHV-6) antigen and to phytohemagglutinin was measured and natural killer (NK) cell activities determined in three consecutive specimens obtained biweekly from 18 young children and infants with exanthema subitum. Virus isolation and PCR detection of virus DNA and determination of neutralization antibody to HHV-6 and -7 were also carried out. The magnitude of the HHV-6 specific lymphoproliferative response varied; however, in most cases the time course kinetics revealed a low response in the acute phase with a subsequent gradual increase. In contrast, NK cell activities were high in the acute phase and declined gradually during convalescence. The lymphoproliferative response to phytohemagglutinin did not show a consistent trend in kinetics of time; however, dynamic changes in activity were observed in patients during the acute and convalescent periods. The results suggest that NK cells play a major role in resolving acute phase infection while specific lymphocyte activity develops later. The cause of the delayed development of HHV-6 specific lymphoproliferative response is unknown. The lymphoproliferative response to phytohemagglutinin ratios implied that HHV-6 infection has some impact on host T-cell immunity during the course of exanthema subitum.

440 Increased TGFβ1 secretion via down-regulating NKG2D killer activator receptor expression results in impaired natural killer cell activity in patients with chronic HCV hepatitis

440 Increased TGFβ1 secretion via down-regulating NKG2D killer activator receptor expression results in impaired natural killer cell activity in patients with chronic HCV hepatitis

Augmentation of lymphokine-activated killer cell activity in patients with gastrointestinal cancer.

Adoptive cellular immunotherapy with lymphokine-(interleukin 2) activated killer (LAK) cells is not as successful in patients with gastrointestinal cancer as with other tumour types. This may be because the cytotoxic capacity of LAK cells from such patients is suboptimal. In this study we have sought to augment this activity by stimulating the lymphocytes with recombinant human interferon-gamma (r-HuIFN-gamma) in addition to interleukin 2 or by depleting the lymphocytes of adherent suppressive mononuclear cells. Both procedures augment LAK activity in gastrointestinal cancer patients but adherent cell depletion results in fewer cells being available for adoptive cellular immunotherapy. No further augmentation of LAK activity of adherent cell depleted cells could be accomplished by addition of r-HuIFN-gamma. Co-stimulation of unfractionated peripheral lymphocytes with r-HuIFN-gamma is the preferable procedure for the generation of LAK cells for adoptive cellular immunotherapy in patients suffering from gastrointestinal cancer.

Increased natural killer cell activity in patients with an abdominal aortic aneurysm

Natural killer (NK) cells have an emerging role in the development of chronic disease and in the direction and maintenance of inflammatory responses. Abdominal aortic aneurysms (AAA) is a chronic inflammatory disorder of unknown aetiology. The aim was to investigate whether NK cells showed altered function in patients with an AAA. The presence, phenotype and function of peripheral blood and tissue NK cells from patients with an AAA, peripheral vascular disease (PVD) and healthy age-sex-matched controls were assessed before and after surgery. Patients with an AAA had significantly higher (P < 0.010) percentages of peripheral blood NK cells (mean (95 per cent c.i.) 23.8 (2.6) per cent) than patients with PVD (17.4 (2.9) per cent) and control subjects (16.2 (2.8) per cent). The NK cells from patients with an AAA had increased cytotoxicity on a per cell basis towards both an NK-sensitive target cell line and human aortic smooth muscle cells. Increased NK cell proportions (22.7 (3.5) per cent) and cytotoxic activity, together with higher C-reactive protein values, persisted after successful AAA repair. These data support the hypothesis that increased NK cytotoxicity could be a contributing factor in the generation or potentiation of inflammation in patients with an AAA.

Loss of natural killer cell activity in patients with coronary artery disease

Background Natural killer (NK) cells are important components of the innate immune system and have a potential role in the regulation of autoimmunity. In the present study, we evaluated the NK cells in patients with coronary artery disease (CAD) and related the findings to clinical and laboratory parameters of the disease. Methods and results We studied 45 patients with acute coronary syndrome (ACS), 50 patients with stable angina and angiographically verified CAD (SA) and 50 healthy controls. The distribution of NK cell subsets was determined by flow cytometry and NK cell-mediated cytotoxicity was quantified ex vivo. Both ACS and SA patients had significantly reduced numbers of CD56 dim NK cells compared with controls. The patients also exhibited a significant decrease in NK cell activity. The loss in NK cell function was not related to inflammatory activity or metabolic status. Conclusion Both stable and unstable conditions of CAD were associated with a redistribution of circulating lymphocytes, comprising a significant reduction of CD56 dim NK cells and a concomitant loss of NK cell function. The findings suggest the presence of a persistent immune aberration in CAD patients independent of their clinical setting or systemic inflammatory state.

Acute effects of electroconvulsive therapy on lymphocyte natural killer cell activity in patients with major depression

Background: Major depression has been associated with a reduction in lymphocyte natural killer cell activity (NKCA). The effects of biological treatment of depression on the immune system have not been systematically investigated. The present study addresses the acute effects of electroconvulsive therapy (ECT) on NKCA. Methods: Thirteen patients undergoing ECT for major depression were studied. NKCA at four different effector:target (E:T) ratios (E:T=50:1; 25:1; 12.5:1 and 6.25:1, respectively) was assessed serially in relation to the first ECT session prior to and up to 1 h following treatment (−30′, −10′, −3′ before ECT and +3′, +10′, +30′ and +60′ following ECT). On several patients, NKCA data were also available in relation to the sixth ECT session. Comparisons between mean NKCA values for each of the E:T ratios at the different time points were made using ANOVA. Results: There were significant changes in NKCA values with time at E:T=25:1 ( P<0.05). Mean NKCA values for the 30 min following ECT were significantly higher than the mean NKCA values for the 30 min preceding ECT for all four E:T ratios used ( P<0.05). Differences in NKCA values between ECT no. 1 and ECT no. 6 were small and not statistically significant. Conclusion: ECT is associated with a significant albeit transient increase in NKCA. The clinical implications of these findings are unknown at the present time. Limitations: A small number of patients has been investigated, particularly for the sixth ECT session. No control group for ECT was available. No correlations with clinical outcome variables have been obtained.

Immunosuppressive effect of chenodeoxycholic acid on natural killer cell activity in patients with biliary atresia and hepatitis C virus-related liver cirrhosis.

Patients with severe liver diseases, such as liver cirrhosis and biliary atresia, have low natural killer (NK) cell activity. The relations between NK activity and measures of liver function, including serum levels of total bilirubin, total bile acids, bile acid components, aspartate aminotransferase, and alanine aminotransferase, and platelet count were examined in patients with biliary atresia (6 boys and 6 girls; mean age, 4.8+/-5.7 years) and patients with liver cirrhosis due to hepatitis C virus infection (10 men and 2 women; mean age, 54.3+/-13.8 years). Univariate analysis showed that platelet count was positively correlated with NK activity in patients with biliary atresia (r = 0.611, P < 0.05). Serum levels of free chenodeoxycholic acid were negatively correlated with NK activity both in patients with biliary atresia (r = -0.647, P < 0.05) and in patients with hepatitis C virus-related liver cirrhosis (r = -0.876, P < 0.01). None of the other free bile acids or conjugated bile acids or other indicators of liver function were correlated with NK activity. Multiple stepwise regression analysis showed that only levels of free chenodeoxycholic acid were independently correlated with NK activity. All patients with biliary atresia underwent liver transplantation from living related donors. NK activity had increased significantly two months after transplantation (from 24.1+/-20.2% to 49.2+/-12.5%, P < 0.01). In contrast, levels of free chenodeoxycholic acid in transplant recipients had decreased significantly two months after transplantation (from 1.22+/-1.16 to 0.26+/-0.21 micromol/l, P < 0.05). In conclusion, in patients with biliary atresia or liver cirrhosis, NK activity in peripheral blood decreases, mostly because of free chenodeoxycholic acid.

Prognostic significance of natural killer cell activity in patients with gastric carcinoma: a multivariate analysis

OBJECTIVE: Natural cytotoxicity, mediated by natural killer (NK) cells, has been believed to play an important role in inhibiting experimental tumor metastasis, and diminished NK cell activities leads to a high incidence of tumor occurrence. Despite convincing evidence from experimental studies, the role of NK cells in the immunological surveillance against cancer in human is poorly defined. METHODS: The present study was based on a retrospective analysis of data on 156 patients with gastric cancer, who were surgically treated in the Department of Surgery II, Kyushu University Hospital from 1993 to 1996. All patients were examined for NK cell activity based on a peripheral blood sampling done preoperatively. RESULTS: Significant association between NK cell activity and clinicopathological parameters including tumor size, lymphatic involvement, vascular involvement, and lymph node metastases was evident. When comparing the two groups according to NK cell activity, tumors with low NK cell activity tend to have lymphatic involvement. The 5-yr survival rates were 94.6% and 72.3% for those with NK cell activity >25% lysis and ≤25% lysis, respectively, the value being statistically significant ( p < 0.05). The independent risk factors for prognosis examined by logistic regression analysis were lymphatic involvement, NK cell activity, depth of tumor invasion, and lymph node dissection. CONCLUSIONS: These current data showed that NK cell activity may be related to tumor volume and dissemination. Measurement of preoperative NK cell activity may be pertinent for the prognosis of patients with gastric cancer and for follow-up clinical management.

Prognostic significance of natural killer cell activity in patients with gastric carcinoma: a multivariate analysis.

Natural cytotoxicity, mediated by natural killer (NK) cells, has been believed to play an important role in inhibiting experimental tumor metastasis, and diminished NK cell activities leads to a high incidence of tumor occurrence. Despite convincing evidence from experimental studies, the role of NK cells in the immunological surveillance against cancer in human is poorly defined. The present study was based on a retrospective analysis of data on 156 patients with gastric cancer, who were surgically treated in the Department of Surgery II, Kyushu University Hospital from 1993 to 1996. All patients were examined for NK cell activity based on a peripheral blood sampling done preoperatively. Significant association between NK cell activity and clinicopathological parameters including tumor size, lymphatic involvement, vascular involvement, and lymph node metastases was evident. When comparing the two groups according to NK cell activity, tumors with low NK cell activity tend to have lymphatic involvement. The 5-yr survival rates were 94.6% and 72.3% for those with NK cell activity > 25% lysis and < or = 25% lysis, respectively, the value being statistically significant (p < 0.05). The independent risk factors for prognosis examined by logistic regression analysis were lymphatic involvement. NK cell activity, depth of tumor invasion, and lymph node dissection. These current data showed that NK cell activity may be related to tumor volume and dissemination. Measurement of preoperative NK cell activity may be pertinent for the prognosis of patients with gastric cancer and for follow-up clinical management.

Serum immunosuppressive acidic protein and natural killer cell activity in patients with metastatic renal cell carcinoma before and after nephrectomy.

To our knowledge the impact of nephrectomy on stage M1 renal cell carcinoma remains to be determined. We previously reported that nephrectomy is beneficial in patients with elevated serum C-reactive protein before treatment, and those in whom nadir C-reactive protein decreases postoperatively to within the normal range may expect longer survival when surgery is combined with postoperative immunotherapy. In this study we determine the effect of nephrectomy on the immune response in patients with metastatic renal cell carcinoma. We retrospectively reviewed the records of 40 patients with metastatic renal cell carcinoma diagnosed at our institution between 1986 and 1999. These patients underwent nephrectomy before cytokine therapy with interferon. Before and after nephrectomy we measured serum C-reactive protein, serum immunosuppressive acidic protein and peripheral blood natural killer cell activity. In 15 patients with pretreatment serum C-reactive protein within the normal range (less than 1 ng./ml.) there was no significant difference before and after nephrectomy in the serum immunosuppressive acidic protein level or natural killer cell activity (p = 0.4587 and 0.3892, respectively). On the other hand, in 25 patients with serum C-reactive protein elevated before treatment to 1 ng./ml. or greater serum immunosuppressive acidic protein decreased significantly and natural killer cell activity increased significantly after cytoreductive surgery (p = 0.0002 and 0.0286, respectively). Our study implies that nephrectomy may be beneficial in patients with elevated serum C-reactive protein before treatment. Further evaluation by a prospective study is needed to make a definitive conclusion.

The effect of clarithromycin treatment on natural killer cell activity in patients with advanced non-small cell lung cancer

The effect of clarithromycin treatment on natural killer cell activity in patients with advanced non-small cell lung cancer

Natural killer cell activity in patients with Graves' disease and Hashimoto's thyroiditis.

Natural killer (NK) cell activity of peripheral blood lymphocytes (PBL) against k562 human tumor cell targets was studied in patients with Graves' disease and Hashimoto's thyroiditis. NK activity was measured in a standard 4-hour 51chromium (Cr) release assay. Cytotoxicity was expressed as lytic units (LU)/10(6) PBL. Significantly decreased NK cell activity was demonstrated in both groups of patients, with mean (+/- SE) lytic units of 10.3 (+/- 9.1) and 13.3 (+/- 10.3) for patients with Graves' disease and Hashimoto's thyroiditis, respectively, compared with 36.0 (+/- 26.3) for age- and sex-matched normal subjects. When patients with Graves' disease were analyzed according to their thyroid status; NK activity was significantly depressed in (1) hyperthyroid patients before treatment; (2) hyperthyroid patients receiving antithyroid therapy; and (3) euthyroid patients receiving antithyroid therapy, compared with normal subjects. Graves' disease patients who were hypothyroid after radioactive iodine therapy or thyroidectomy had normal NK activity. No significant differences between hyperthyroid and euthyroid patients or between hypothyroid patients and normal subjects were demonstrated. NK activity in patients with Graves' disease did not correlate with serum levels of thyroxine, the presence or severity of ophthalmopathy, or titers of serum thyroid antibodies. In patients with Hashimoto's thyroiditis there was no correlation between NK activity and goiter size, titers of antithyroid antibodies, or thyroid status. These findings suggest that depression of NK activity in both disorders is secondary to abnormalities of thyroid hormone secretion, although an effect of the underlying autoimmune reactions has not been excluded.

Prognostic significance of natural killer cell activity in patients with laryngeal carcinoma.

For laryngeal carcinoma, the present TNM clinical staging system does not seem completely satisfactory as a guide for providing a prognosis for survival. We believe that natural killer cell activity would probably have a role in a more reliable system. Therefore, we analyzed the disease outcome with previously untreated epidermoid carcinoma of the larynx, evaluating classic clinical and pathologic factors, as well as natural killer cell activity in peripheral blood samples of the patients. To determine the level of natural killer cell activity in patients with laryngeal carcinoma and to analyze the prognostic value of this finding when associated with other clinical and pathologic variables. Prospective cohort study of surveillance of laryngeal cancer. Mean follow-up of 42.8 months. Tertiary care referral center and ambulatory and hospitalized care. We compared 81 men (mean age, 62.4 years; range, 35-89 years) with laryngeal carcinoma with 44 healthy men serving as control subjects (mean age, 57.6 years; range, 37-82 years). Natural killer cell activity was significantly reduced in patients who had died of cancer-related causes in comparison with tumor-free survivors. Overall actuarial survival differed significantly in histologically assessed nodal involvement and low natural killer cell activity. Use of the Cox proportional hazards regression model showed that the factors that seem to have a prognostic effect on survival are histologically determined nodal involvement and low natural killer cell activity. These results support the prognostic significance of the determination of pretreatment natural killer cell activity in peripheral blood samples from patients with laryngeal carcinoma and suggest that assessment of adding such a determination to the current tumor staging system is advisable.