Natural Killer T Cells (NKT cells) Functions in Malignancies

Background/aim: Natural killer (NK) cell receptors affect the NK cell-mediated elimination of malignant cells. In this experimental study the effect of Zoledronic acid (ZOL) was investigated on the expression of NK activating-(NKP46 and NKG2D) and inhibitory (KIR2DL1) receptors by Phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from breast cancer (BC) patients. Materials and Methods: Peripheral blood mononuclear cell-extracted RNA from thirty breast cancer women and twenty-five healthy subjects was analyzed for gene expression of NKP46, NKG2D and KIR2DL1 using real time-PCR. Then, the PBMCs from BC patients were cultured in the presence of PHA with 5 μg/ml, 10 or 20 μg/ml of ZOL for 32 hours and expression of the aforementioned receptors was determined. Results: Expression of NKP46, NKG2D and NKP46/KIR2DL1 ratio in BC women were lower than healthy group (P<0.01, P<0.04 and P<0.05, respectively). NKP46 expression was up-regulated by PHA-stimulated PBMCs treated with 10 μg/ml and 20 μg/ml of ZOL compared with PHA-stimulated cultures (P<0.01 and P<0.05, respectively). NKG2D expression remarkably increased by PHA-stimulated cultures treated with 5 μg/ml, 10 μg/ml and 20 μg/ml of ZOL compared with PHA-stimulated cultures (P<0.05 and P<0.02 and P<0.04, respectively). Conclusion: Expression of NK cell-related activating receptors decreased in BC patients. ZOL can improve the expression of NK activating receptors.

Section: Reduced Expression Of Natural Killer Cell-related Activatingmentioning

confidence: 99%

Reduced Expression of Natural Killer Cell-Related Activating Receptors by Peripheral Blood Mononuclear Cells from Patients with Breast Cancer and Their Improvement by Zoledronic Acid

Rahimian

Khandani

Nemati

et al. 2022

“…In the tumor microenvironment, anti-tumor immunity is related to infiltrating immune cell crosstalk with each other and with adjacent tumor cells (Balouchi-Anaraki and Nourozian, 2018). Therefore, studying different HCC immuno-landscapes could provide promising therapeutic…”

Section: Introductionmentioning

confidence: 99%

The Putative Role of Natural Killer Cells in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma

Hassouna

Radwan

Abdelsameea

et al. 2021

Background: Natural Killer (NK) cells have crucial roles in immune responses against malignant transformation including hepatocellular carcinoma (HCC). The NKG2D receptor has a critical role in the NK recognition of target cells. Aim: We assessed NKG2D receptor expression as a diagnostic biomarker for HCC detection and progression in Egyptian patients with hepatitis C virus (HCV)-related HCC. Methods: We classified 81 patients into three groups: chronic hepatitis (21), cirrhotic (30) and HCC (30) patients, with 36 individuals enrolled to the control group. We analyzed NK levels in peripheral blood and NKG2D receptor expression in NK cells using flow cytometry. Results: We observed a significant decrease in NKG2D (CD314) expression on circulating NK cells and frequency of NK cells expressing NKG2D (CD314) in HCC patients. Also, in patients, larger foci lesions significantly correlated with decreased NK cell numbers. Multiple foci numbers and patients with a Child score C significantly correlated with decreased circulating NK cells expressing NKG2D and decreased NKG2D expression. Conclusion: The percentage of NK cells in peripheral blood and NKG2D receptor expression could function as potential biomarkers for HCC detection and progression.

“…Another component which contributes to the scenario is the involvement of inflammatory factors, such as cytokines. Recently, it was shown, that NKT cells play key role in malignancies through their ability to rapidly produce a large amount of pro-inflammatory cytokines (Balouchi-Anaraki S et al, 2018). Indeed, smoking is also involved because it was reported to induce inflammatory responses and obstruction of airways, and to be associated with COPD (Caramori et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Involvement of Circulating Cell-Free Mitochondrial DNA and Proinflammatory Cytokines in Pathogenesis of Chronic Obstructive Pulmonary Disease and Lung Cancer

Bulgakova

Kausbekova

Kussainova

et al. 2021

Objective: Circulating cell-free mitochondrial DNA (cf-MtDNA) has been reported in patients with chronic obstructive pulmonary disease (COPD) and lung cancers. However, inter-relationships among the three biological events have not been well-characterized. Therefore, our investigation was conducted to better understand the role of cf-MtDNA on pathogenesis of the two diseases. Methods: Plasma samples were collected from 64 non-small cell lung cancer (NSCLC) patients (before therapy), 45 patients with COPD and 62 healthy individuals. cf-MtDNA copy numbers were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and cytokines were determined using a human ELISA kit. Results: Our data indicate that smoking statuses of the patients and controls were significantly associated with increased cf-MtDNA in plasma samples. Furthermore, NSCLC patients had significantly higher cf-MtDNA copy numbers than COPD patients (p < 0.03) and normal controls (p < 0.02), together with elevated proinflammatory cytokines over the controls (p < 0.05). Our study shows that the copy numbers for the NSCLC patients were positively associated with their subsequent metastasis but inversely associated with their overall survival. Conclusion:Our study indicates certain lung injury (e.g., from cigarette smoking) was responsible for the release of cf-MtDNA and proinflammatory cytokines into plasmas among our patients and controls. The increase in cf-MtDNA copy numbers was significantly associated with the development of both COPD and NSCLC, with increase in interleukin 6, and from our 5-year follow-up, with poor prognosis among the NSCLC patients. Therefore, with further validation, cf-MtDNA can be considered for use as diagnostic and prognostic biomarkers for NSCLC.