NK Cells: Immune Cross-Talk and Therapeutic Implications

Malhotra, Anshu; Shanker, Anil

doi:10.2217/imt.11.102

Cited by 95 publications

(72 citation statements)

References 245 publications

(259 reference statements)

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“…The main triggering activating receptors expressed by NK cells include CD16, NKG2D, NKG2C, CD226 (DNAM-1), CD244 (2B4) and the natural cytotoxicity receptors. 18,24 The ligands for the activating receptor NKG2D are cellular stress inducible molecules: MICA, MICB, and ULBPs. 25 The main inhibitory receptors are killer cell immunoglobulin-like receptors (KIRs), CD94/NKG2A and leukocyte immunoglobulin-like receptor 1 (CD85), most of which recognize MHC class I molecules.…”

Section: Nk Receptors In Tumorsmentioning

confidence: 99%

“…[22][23][24][25]58 The immunosuppressive cytokine TGF-b and the cells that are its main source, Treg cells, have been reported to downregulate surface expression of NKG2D and other activating NK cell receptors in the tumor microenvironment, thereby impairing NK cell function and further promoting tumor progression. 46,68 PGE2 and IDO derived from tumor cells can also downregulate NKG2D expression.…”

Section: Downregulated Activating Receptorsmentioning

confidence: 99%

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NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

et al. 2014

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Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. There is a significant correlation between chronic hepatitis B virus (HBV) infection and hepatocarcinogenesis. As the first line of host defense against viral infections and tumors, natural killer (NK) cells express a large number of immune recognition receptors (NK receptors (NKRs)) to recognize ligands on hepatocytes, liver sinusoidal endothelial cells, stellate cells and Kupffer cells, which maintain the balance between immune response and immune tolerance of NK cells. Unfortunately, the percentage and absolute number of liver NK cells decrease significantly during the development and progression of HCC. The abnormal expression of NK cell receptors and dysfunction of liver NK cells contribute to the progression of chronic HBV infection and HCC and are significantly associated with poor prognosis for liver cancer. In this review, we focus on the role of NK cell receptors in anti-tumor immune responses in HCC, particularly HBV-related HCC. We discuss specifically how tumor cells evade attack from NK cells and how emerging understanding of NKRs may aid the development of novel treatments for HCC. Novel mono-and combination therapeutic strategies that target the NK cell receptor-ligand system may potentially lead to successful and effective immunotherapy in HCC. Keywords: activating receptor; hepatocellular carcinoma; inhibitory receptor; natural killer cell; natural killer receptor INTRODUCTION Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. 1 Common clinical risk factors for HCC include hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, heavy alcohol intake, steatohepatitis and diabetes. 2 Approximately 50% of HCC cases worldwide can be attributed to chronic HBV infection (CHB) and almost 75% of HCC cases occur in developing countries where HBV is endemic. 3,4 According to statistics, older male patients who are infected with HBV genotype C or co-infected with HCV, have high levels of viral load and have been exposed to the aflatoxin, or older male patients who have a family history of HCC tend to have a high risk of developing HCC. [5][6][7] Accumulating clinical and epidemiological evidence shows a significant correlation between chronic HBV infection and hepatocarcinogenesis. However, the underlying mechanisms

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Section: Nk Receptors In Tumorsmentioning

confidence: 99%

Section: Downregulated Activating Receptorsmentioning

confidence: 99%

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

et al. 2014

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“…bortezomib, triterpenoids) which enhance the tumour’s sensitivity to directly administered death ligand proteins or agonist antibodies [288,289], or immune cells providing a natural source of death ligands [290], or reduce tumour resistance to effector CD8 + T cells following adoptive transfer. Furthermore, a close collaboration of the innate and adoptive components of the immune system should be emphasized in view of the more recent work in different immune conditions [291] showing their interdependent synergy for an optimal anti-tumour immune response. An optimal clinical protocol should attempt to combine those strategies with complementary immunostimulatory schemes, which can overcome the tumour-associated immunosuppression, such as stimulation of Notch signalling in lymphopoietic cells by immunopotentiating Notch ligand formulations [107,292,293].…”

Section: Discussionmentioning

confidence: 99%

Challenges and future perspectives of T cell immunotherapy in cancer

et al. 2015

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Since the formulation of the tumour immunosurveillance theory, considerable focus has been on enhancing the effectiveness of host antitumour immunity, particularly with respect to T cells. A cancer evades or alters the host immune response by various ways to ensure its development and survival. These include modifications of the immune cell metabolism and T cell signaling. An inhibitory cytokine milieu in the tumour microenvironment also leads to immune suppression and tumour progression within a host. This review traces the development in the field and attempts to summarize the hurdles that the approach of adoptive T cell immunotherapy against cancer faces, and discusses the conditions that must be improved to allow effective eradication of cancer.

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“…The inhibitory receptors encompass two distinct classes: the monomeric type I glycoprotein of the immunoglobulin superfamilies KIR2DL and KIR3DL [51], leukocyte immunoglobulinlike receptors (ILT2), and the hetero-dimeric C-type lectin-like receptor (CTLR) called CD94/ NKG2A (natural killer group protein 2 family member A) [52,53].…”

Section: Inhibitory Nk Cell Receptorsmentioning

confidence: 99%

NK Cells in Cancer Immunotherapy

Addou-Klouche¹

2017

Natural Killer Cells

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Natural killer (NK) cells are crucial components of the innate immune system and play critical roles in host immunity against viral infections and cancer. NK cells' activity is controlled by the interaction of a wide range of receptors expressed on their surfaces with cell surface ligands. Opposite signals delivered by inhibitory and activating receptors tightly regulate NK cells' cytotoxicity. Natural killer cells can discriminate between normal and cancer cells. NK cells are known to directly recognize and kill malignant cells or induce apoptosis. However, tumor cells have the ability to evade those atacks.The main mechanisms involve the lack of expression or downregulation of the expression of major histocompatibility complex (MHC) class I molecules and secretion of soluble NKG2D ligands by tumor cells. Furthermore, tumors harbor a population of cancer stem cells (CSCs), which can drive tumor progression and therapeutical resistance. This chapter highlights the roles of NK cells in tumor immunosurveillance and their applications for cancer immunotherapy. NK cell biology and function as well as the role of their receptor interactions will be described. We will discuss the therapeutic applications of NK cells in cancer and NK cells targeting CSCs as a promising strategy for cancer therapy.

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NK Cells: Immune Cross-Talk and Therapeutic Implications

Cited by 95 publications

References 245 publications

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

Challenges and future perspectives of T cell immunotherapy in cancer

NK Cells in Cancer Immunotherapy

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