Cybermedlife - Therapeutic Actions NK Cell Activity

Natural killer cells preferentially target cancer stem cells; role of monocytes in protection against NK cell mediated lysis of cancer stem cells. 📎

Abstract Title: Natural killer cells preferentially target cancer stem cells; role of monocytes in protection against NK cell mediated lysis of cancer stem cells. Abstract Source: Curr Drug Deliv. 2012 Jan ;9(1):5-16. PMID: 22023212 Abstract Author(s): Anahid Jewett, Han-Ching Tseng, Aida Arasteh, Saba Saadat, Russell E Christensen, Nicholas A Cacalano Article Affiliation: The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, Los Angeles, CA 90095-1668, USA. This email address is being protected from spambots. You need JavaScript enabled to view it. Abstract: Mounting effective anti-tumor immune responses by cytotoxic effectors is important for the clearance of tumors. However, accumulated evidence suggests that the cytotoxic function of immune effectors is largely suppressed in the tumor microenvironment by a number of distinct effectors and their secreted factors. The aims of this review are to provide a rationale and potential mechanism for immunosuppression in cancer, and to demonstrate the significance of such immunosuppression in cellular differentiation and tissue regeneration in pathological conditions, and progression of cancer. We have recently shown that increased NK cell function was seen when they were cultured with primary oral squamous carcinoma stem cells (OSCSCs) as compared to their more differentiated oral squamous carcinoma cells (OSCCs). In addition, human embryonic stem cells (hESCs), Mesenchymal Stem Cells (hMSCs), dental pulp stem cells (hDPSCs) and induced pluripotent stem cells (hiPSCs) were significantly more susceptible to NK cell mediated cytotoxicity than their differentiated counterparts or parental cells from which they were derived. We have also reported that inhibition of differentiation or reversion of cells to a less-differentiated phenotype by blocking NFκB or targeted knock down of COX2 augmented NK cell function significantly. Total population of monocytes and those depleted of CD16(+) subsets were able to substantially prevent NK cell mediated lysis of OSCSCs, MSCs and DPSCs. Taken together, our results suggest that stem cells are significant targets of the NK cell cytotoxicity. The concept of split anergy in NK cells and its contribution to tissue repair and regeneration and in tumor resistance and progression will be discussed in this review. Therefore, patients with cancer may benefit from repeated allogeneic NK cell transplantation atthe site of the tumor for specific elimination of cancer stem cells. Article Published Date : Dec 31, 2011
Therapeutic Actions NK Cell Activity

NCBI pubmed

Human Leukocyte Antigen-G (HLA-G) Expression in Precancerous and Cancerous Cervical Lesions: Association with Human Papilloma Virus Infection and Host Immune Response.

Related Articles Human Leukocyte Antigen-G (HLA-G) Expression in Precancerous and Cancerous Cervical Lesions: Association with Human Papilloma Virus Infection and Host Immune Response. Egypt J Immunol. 2018 Jan;25(1):125-134 Authors: Fahim NM, Shehata IH, Taha SE, Fahmy RA, Elsayed MS Abstract Human leukocyte antigen-G (HLA-G) is a non-classical HLA-class Ib molecule with multiple immunoregulatory properties. Its main functions in physiological conditions are to abolish maternal immune cell activity against fetus and to establish immune tolerance at the maternal-fetal interface. Cervical tumor cells have been reported to express HLA-G which is one of the immunomodulatory molecules that is involved in every phase of cancer immunoediting. It has inhibitory functions against natural killer (NK) cells, T-lymphocytes, and antigen-presenting cells (APCs). The purpose of this study was to investigate the HLA-G expression in precancerous (squamous intraepithelial cervical lesion) and cancer cervix and determine HLA-G expression relation to HPV infection as well as host immune response. The study included 48 paraffin embedded cervical tissue sections [32 squamous intraepithelial lesion (SIL) {16 low grade lesions (LSIL) and 16 high grade lesions (HSIL)} and 16 cervical cancer tissue sections]. All tissue sections were examined for HLA-G expression by real time PCR and for host immune response by estimating the number of tumor infiltrating lymphocyte (TIL) and NK CD57+ cells. HLA-G expression increased progressively from precancerous and cancerous cervical lesions. There was an inverse relationship between HLA-G expression and estimated number of TILs and NK CD57+ cells. No significant statistical difference between HPV positive and HPV negative cervical lesions as regards HLA-G expression was detected. In conclusion, HLA-G is a potential biomarker for the diagnosis and prognosis of cervical cancer as there was a progressive increase in expression of HLA-G in precancerous and cancerous cervical lesion. It is functionally involved in tumor escape mechanisms as observed by inhibition of host immune response and more studies are needed to design strategies for blockade of HLA G expression or elimination of HLA G expressing cancer cells as this may be important to the efficacy of anticancer therapies. PMID: 30243004 [PubMed - in process]

Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis.

Related Articles Effect of bevacizumab plus XELOX (CapeOX) chemotherapy on liver natural killer cell activity in colorectal cancer with resectable liver metastasis. Ann Gastroenterol Surg. 2018 Sep;2(5):383-393 Authors: Hirata F, Ishiyama K, Tanaka Y, Kobayashi T, Hashimoto M, Saeki Y, Ishida N, Taguchi K, Tanaka J, Arihiro K, Ohdan H, Hiroshima Surgical Study Group of Clinical Oncology (HiSCO) Abstract Aim: We investigated the chemotherapy effect of resectable colorectal cancer with liver metastasis (CRLM) on the function of intrahepatic immune cells. Methods: We classified patients into adjuvant chemotherapy (bevacizumab+CapeOX) after hepatectomy group (group A) and neoadjuvant chemotherapy followed by hepatectomy group (group B), and collected peripheral blood mononuclear cells (PBMC) and liver mononuclear cells (LMNC) to ascertain phenotypic and functional differences. Results: There were no significant differences in lymphocyte fractions of either PBMC or LMNC between groups, except for the significantly lower percentage of natural killer (NK) cells in LMNC in group B than in group A. Significantly higher percentage of natural-killer group 2, member D (NKG2D)- positive NK cells in PBMC and percentage of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-, NKp30-, and signal regulatory protein β (SIRPβ)-positive NK cells in LMNC were found in group B. Furthermore, significantly higher expressions of NKG2D and SIRPβ in peripheral blood NK cells and of NKp46 and CD122 in liver NK cells were found in group B. When LMNC were incubated with interleukin (IL)-2 in vitro, no difference was observed in the expression of these molecules in NK cells between groups. Consistently, there was no difference in the cytotoxic activity of those LMNC against a colon adenocarcinoma cell line between groups. Conclusion: Colorectal cancer with liver metastasis patients treated with neoadjuvant chemotherapy showed enhanced expression of activation markers on peripheral blood and liver NK cells in comparison with patients who did not receive therapy; however, the difference in those function remains unclear. These results suggest that neoadjuvant chemotherapy does not have a negative impact on intrahepatic immune cells in resectable CRLM patients. PMID: 30238080 [PubMed]

Effects of polychlorinated biphenyls (PCB) on California sea lion (Zalophus californianus) lymphocyte functions upon in vitro exposure.

Related Articles Effects of polychlorinated biphenyls (PCB) on California sea lion (Zalophus californianus) lymphocyte functions upon in vitro exposure. Environ Res. 2018 Aug 24;: Authors: Peñín I, Levin M, Acevedo-Whitehouse K, Jasperse L, Gebhard E, Gulland FMD, De Guise S Abstract Polychorinated biphenyl (PCB) congeners are a cause for concern due to their persistence in the environment, their lipophilic properties that cause them to bio-accumulate in top predators, and their adverse effects on mammalian health. For example, the common urogenital carcinoma reported in California sea lions (Zalophus californianus) (CSL) is associated with high tissue levels of PCBs, but the mechanisms responsible for this association are unknown. This study investigated the effect of exposure to six PCB congeners and a congener mix at low and environmentally relevant concentrations on NK cell-like and T cell activity using in vitro assays on cryopreserved lymph node mononuclear cells isolated from dead CSL. Non dioxin-like congeners 153 and 180 increased lymphocyte proliferation at 5 and 10 ppm, while congener 138 decreased proliferation by up to 43% at 15 ppm. Dioxin-like PCBs 118 and 169 did not affect lymphocyte proliferation, while the effects of congener 105 depended on the mitogen concentration; these did not correlate with their predicted toxic equivalent factors. NK cell-like activity was affected only by the highest concentration of PCBs tested; it was increased by non-dioxin-like congeners 138 and 153, and decreased by dioxin-like congener 169. The PCB congener mix suggested that the effects of PCB congeners were not simply additive. Our results concur with effects of PCBs reported for other pinniped's lymphocytes and add further experimental support to the observation that dioxin-like PCBs are not the most toxic congeners for marine mammals, contrary to effects in other species. This is the first evidence of in vitro suppression of NK cell-like cytotoxicity by a dioxin-like congener in a pinniped. More importantly, the observed results suggest that PCBs can modulate the CSL immune system, increasing exposed individuals' susceptibility to viral and oncogenic challenges. PMID: 30236520 [PubMed - as supplied by publisher]

The Effect of Pectinase-Assisted Extraction on the Physicochemical and Biological Properties of Polysaccharides from Aster scaber.

Related Articles The Effect of Pectinase-Assisted Extraction on the Physicochemical and Biological Properties of Polysaccharides from Aster scaber. Int J Mol Sci. 2018 Sep 19;19(9): Authors: Song YR, Sung SK, Shin EJ, Cho CW, Han CJ, Hong HD Abstract The edible and medicinal perennial herb Aster scaber is known to have anticancer, antioxidant, and immunomodulatory properties. However, the biological effects of its polysaccharides are not well understood. Here, we aimed to extract novel polysaccharides with enhanced biological properties from Aster scaber using enzyme-assisted methods. Amylase, cellulase, and pectinase were used to extract enzyme-assisted polysaccharide (ASEP)-A, ASEP-C, and ASEP-P, respectively. The yields, physicochemical properties, and immunostimulatory activities of the polysaccharides were investigated and compared with those of hot water extracted polysaccharide (ASWP). The highest yield (3.8%) was achieved for ASEP-P extracted using pectinase digestion. Fourier-transform infrared spectroscopy (FT-IR) and chemical composition analysis revealed that ASWP and three ASEPs were typical acidic heteropolysaccharides, mainly comprising rhamnose, arabinose, galactose, glucose, and galacturonic acid. Immunostimulatory activity assays on RAW264.7 macrophages showed ASEP-P to have the greatest immunostimulatory potential in terms of nitric oxide (NO) and cytokine productions and phagocytic activity. ASEP-P administration improved immune-enhancing effects in normal mice by improving the spleen index and splenic lymphocyte proliferation, and in immunosuppressed mice by modulating lymphocyte proliferation, natural killer (NK) cell activity, and leukocyte counts. The ASEP-P derived from pectinase hydrolysate of Aster scaber demonstrated efficacious immunostimulatory properties and has potential applications as an immune stimulator. PMID: 30235870 [PubMed - in process]

Robust Innate Immunity of Young Rabbits Mediates Resistance to Rabbit Hemorrhagic Disease Caused by Lagovirus Europaeus GI.1 But Not GI.2.

Related Articles Robust Innate Immunity of Young Rabbits Mediates Resistance to Rabbit Hemorrhagic Disease Caused by Lagovirus Europaeus GI.1 But Not GI.2. Viruses. 2018 09 19;10(9): Authors: Neave MJ, Hall RN, Huang N, McColl KA, Kerr P, Hoehn M, Taylor J, Strive T Abstract The rabbit caliciviruses Lagovirus europaeus GI.1 and GI.2 both cause acute necrotizing hepatitis in European rabbits (Oryctolagus cuniculus). Whilst GI.2 is highly virulent in both young and adult rabbits, rabbits younger than eight weeks of age are highly resistant to disease caused by GI.1, although they are still permissive to infection and viral replication. To investigate the underlying mechanism(s) of this age related resistance to GI.1, we compared liver transcriptomes of young rabbits infected with GI.1 to those of adult rabbits infected with GI.1 and young rabbits infected with GI.2. Our data suggest that kittens have constitutively heightened innate immune responses compared to adult rabbits, particularly associated with increased expression of major histocompatibility class II molecules and activity of natural killer cells, macrophages, and cholangiocytes. This enables them to respond more rapidly to GI.1 infection than adult rabbits and thus limit virus-induced pathology. In contrast, these responses were not fully developed during GI.2 infection. We speculate that the observed downregulation of multiple genes associated with innate immunity in kittens during GI.2 infection may be due to virally-mediated immunomodulation, permitting fatal disease to develop. Our study provides insight into the fundamental host⁻pathogen interactions responsible for the differences in age-related susceptibility, which likely plays a critical role in defining the success of GI.2 in outcompeting GI.1 in the field. PMID: 30235853 [PubMed - in process]