Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population

Imai, Kazue; Matsuyama, Satoru; Miyaké, Satoshi; Suga, Kenji; Nakachi, Kei

doi:10.1016/s0140-6736(00)03231-1

Cited by 1,009 publications

(739 citation statements)

References 15 publications

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“…[38][39][40][41] An 11-year follow-up study in patients indicated that low NK-like cytotoxicity was associated with increased cancer risk. 42 High levels of tumor infiltrating NK cells (TINKs) are associated with a favorable tumor outcome in patients with colorectal carcinoma, gastric carcinoma and squamous cell lung cancer, suggesting that NK-cell infiltration into tumor tissues represents a positive prognostic marker. [43][44][45] As described above, NK-cell recognition of tumor cells by inhibitory and activating receptors is complex, and the three recognition models-'missing-self', 'non-self' and 'stress-induced self'-might be used to sense missing-or altered-self cells.…”

Section: Conception Of Nk Cellsmentioning

confidence: 99%

NK cell-based immunotherapy for malignant diseases

et al. 2013

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Natural killer (NK) cells play critical roles in host immunity against cancer. In response, cancers develop mechanisms to escape NK cell attack or induce defective NK cells. Current NK cell-based cancer immunotherapy aims to overcome NK cell paralysis using several approaches. One approach uses expanded allogeneic NK cells, which are not inhibited by self histocompatibility antigens like autologous NK cells, for adoptive cellular immunotherapy. Another adoptive transfer approach uses stable allogeneic NK cell lines, which is more practical for quality control and large-scale production. A third approach is genetic modification of fresh NK cells or NK cell lines to highly express cytokines, Fc receptors and/or chimeric tumor-antigen receptors. Therapeutic NK cells can be derived from various sources, including peripheral or cord blood cells, stem cells or even induced pluripotent stem cells (iPSCs), and a variety of stimulators can be used for large-scale production in laboratories or good manufacturing practice (GMP) facilities, including soluble growth factors, immobilized molecules or antibodies, and other cellular activators. A list of NK cell therapies to treat several types of cancer in clinical trials is reviewed here. Several different approaches to NK-based immunotherapy, such as tissue-specific NK cells, killer receptor-oriented NK cells and chemically treated NK cells, are discussed. A few new techniques or strategies to monitor NK cell therapy by non-invasive imaging, predetermine the efficiency of NK cell therapy by in vivo experiments and evaluate NK cell therapy approaches in clinical trials are also introduced.

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Section: Conception Of Nk Cellsmentioning

confidence: 99%

NK cell-based immunotherapy for malignant diseases

et al. 2013

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“…10 We have been interested in addressing the still highly contentious issue of whether the immune system contributes to immune surveillance of cancer in humans. Traditional epidemiological approaches to studying PRF deficiency and cancer susceptibility are virtually impossible, 85 as bi-allelic PRF1 mutations are extremely rare, and bone marrow reconstitutions make meaningful follow-up studies on PRF biology impossible. However, in a breakthrough study, Clementi et al 76 investigated the presence of PRF mutations in a group of 29 primary lymphoma patients and found four individuals with bi-allelic PRF1 mutations, all of who developed cancer beyond the age of 7 years.…”

Section: Perforin Deficiency and Human Cancermentioning

confidence: 99%

Perforin deficiency and susceptibility to cancer

et al. 2010

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Cytotoxic lymphocytes (CLs) are the killer cells that destroy intracellular pathogen-infected and transformed cells, predominantly through the cytotoxic granule-mediated death pathway. Soluble cytotoxic granule components, including pore-forming perforin and pro-apoptotic serine proteases, granzymes, synergize to induce unscheduled apoptosis of the target cell. A complete loss of CL function results in an aggressive immunoregulatory disorder, familial hemophagocytic lymphohistiocytosis, whereas a partial loss of function seems to be a factor strongly predisposing to hematological malignancies. This review discusses the pathological manifestations of CL deficiencies due to impaired perforin function and describes novel aspects of perforin biology. Cell Death and Differentiation (2010) 17, 607-615; doi:10.1038/cdd.2009; published online 15 January 2010Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, collectively called cytotoxic lymphocytes (CLs), kill virusinfected and transformed cells through a number of contactdependent mechanisms. 1,2 Engagement of death receptors by membrane-bound members of the TNF superfamily of death ligands is critical for maintaining lymphoid homeostasis in the host. By contrast, studies of gene deficiencies indicate that defects of the granule exocytosis pathway result in a failure to eliminate infected cells or those that pose a risk of subsequent malignancy. Although cytotoxic granules contain diverse toxins that together contribute to apoptosis induction, this review will deal exclusively with the critical role of the pore-forming protein perforin (PRF) as an essential enabler of target-cell apoptosis, and its more recently described role as a potential 'extrinsic' tumor suppressor.Perforin is a 67-kDa pore-forming protein that is stored and released from the secretory granules (SGs) of CLs along with a number of pro-apoptotic serine protease granzymes that display broad substrate specificities. 3 Following exocytic release, PRF and the granzymes are exposed to the neutral pH and calciumrich environment of the immune synapse. 4 After binding calcium through their C2 domains, PRF monomers acquire the ability to bind generic lipids in the target cell membrane, 5 and then coalesce into large transmembrane pores that permit the granzymes to access key death substrates in the cytosol. [6][7][8] Although the diverse apoptotic pathways triggered by granzymes have been extensively studied and are now understood in considerable detail, it is only of late that insights into the molecular and cellular functions of PRF have been even partly addressed.In this review, we will re-examine the pathological consequences of PRF deficiency, both in mice and humans. In doing so, important differences in PRF biology between these species will be described. We will discuss the pathogenic effect of a number of recently described missense mutations of human PRF. In particular, although the complete absence of PRF function typically results in an aggressive, fatal immunoregulatory disorder of ea...

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“…NK cells also play an important role in inhibiting experimental tumor metastasis [11][12][13]. In humans, an 11-year follow-up epidemiologic survey showed that the level of NK cell activity in peripheral blood was associated with cancer risk in adults; low NK cell activity was associated with increased cancer risk [14].…”

Section: Introductionmentioning

confidence: 99%

Decreased NKG2D expression on NK cells correlates with impaired NK cell function in patients with gastric cancer

2011

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Background Although malignant diseases are known to be associated with immune suppression, the detailed mechanisms involved are still unknown. NKG2D is an activating cell surface receptor expressed by natural killer (NK) cells and CD8? T cells, and the engagement of NKG2D is extremely important for NK cell activation. Although decreased NKG2D expression on NK cells is closely related to immune evasion by some cancers, the immunopathological importance of this phenomenon in gastric cancer patients remains unclear. Methods NKG2D expression on NK cells was determined, using multicolor flow cytometry, to investigate the mechanisms responsible for immune evasion in gastric cancer patients. Results NKG2D expression on NK cells from gastric cancer patients was significantly lower than that in healthy controls. Also, NKG2D expression in advanced gastric cancer was significantly lower than that in early gastric cancer. NK cells from patients with lymph node metastasis expressed significantly lower levels of NKG2D than the NK cells from those without lymph node metastasis, and NKG2D expression on NK cells in gastric cancer tissue was significantly lower than that of circulating NK cells. NKG2D expression on NK cells obtained from cancer patients was restored after 48 h in culture with RPMI containing 10% AB serum. Furthermore, NKG2D expression on NK cells obtained after surgery was significantly higher than that before surgery.Conclusions Decreased NKG2D expression on NK cells may be one of the key mechanisms responsible for NK cell dysfunction in gastric cancer.

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Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population

Cited by 1,009 publications

References 15 publications

NK cell-based immunotherapy for malignant diseases

NK cell-based immunotherapy for malignant diseases

Perforin deficiency and susceptibility to cancer

Decreased NKG2D expression on NK cells correlates with impaired NK cell function in patients with gastric cancer

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