Melanoma Cells Inhibit Natural Killer Cell Function by Modulating the Expression of Activating Receptors and Cytolytic Activity

Pietra, Gabriella; Manzini, Claudia; Rivara, Silvia; Vitale, Massimo; Cantoni, Claudia; Petretto, Andrea; Balsamo, Mirna; Conte, Romana; Benelli, Roberto; Minghelli, Simona; Solari, Nicola; Gualco, Marina; Queirolo, Paola; Moretta, Alessandro; Mingari, Maria Cristina

doi:10.1158/0008-5472.can-11-2544

Cited by 267 publications

(222 citation statements)

References 47 publications

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“…Additionally, tumours themselves secrete immunomodulatory molecules that compromise the activity of immune cells in general, and NK cells in particular. Factors that can suppress NK cell effector functions include TGFβ 79 , prostaglandin E 2 (REFS 80,81), indoleamine 2,3-dioxygenase 81 and adenosine 82 (FIG. 2).…”

Section: Nk Cell Functionsmentioning

confidence: 99%

NK cells and cancer: you can teach innate cells new tricks

2015

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Section: Nk Cell Functionsmentioning

confidence: 99%

NK cells and cancer: you can teach innate cells new tricks

2015

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“…46,68 PGE2 and IDO derived from tumor cells can also downregulate NKG2D expression. 69,70 Elevated levels of sMICA are associated with downregulated NKG2D expression and impaired activation of NK cells in advanced HCC patients. 66 Another suppressive cell, the myeloid-derived suppressor cell, in patients with HCC NK cell receptor imbalance and NK cell dysfunction C Sun et al induced NK cell dysfunction characterized by impaired cytotoxicity and cytokine secretion.…”

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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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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“…These ligands may also induce apoptosis of immune effector cells by activating cytotoxic T lymphocytes, thus functioning in tumor-mediated counterattack. 17,18 MELANOMA AND THE SUN The medical literature shows a consensus that extensive exposure to UV radiation is a risk factor for melanoma. 19 Although the exact mechanism is not clear, experts have speculated that the combination of carcinogenic, inflammatory, and immunosup-…”

Section: The Melanoma Microenvironmentmentioning

confidence: 99%

Melanoma in Immunosuppressed Patients

Kubica

Brewer

2012

Mayo Clinic Proceedings

115

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The immunogenic characteristics of malignant melanoma are intriguing. To date, multiple studies exist regarding the immunogenicity of melanoma. In this article, we summarize data in the literature on the role of immunosuppression in melanoma and discuss several immunocompromised patient populations in detail. A comprehensive PubMed search was conducted with no date limitation. The following search terms were used: melanoma in combination with immunosuppression, immunocompromised, genetics, antigen processing, UV radiation, organ transplantation, organ transplant recipients, lymphoproliferative disease, lymphoma, CLL, NHL, radiation, and HIV/AIDS. Although no formal criteria were used for inclusion of studies, most pertinent studies on the topic were reviewed, with the exception of smaller case reports and case series. The included studies were generally large (Ն1000 patients in organ transplant recipient studies; Ն500 patients in lymphoma studies), with a focus on institutional experiences, or population-based national or international epidemiologic studies. Melanoma-induced immunosuppression, the role of UV radiation in melanoma development, and the epidemiology, clinical course, and prognosis of melanoma in immunocompromised patients are highlighted. Organ transplant recipients, patients with lymphoproliferative disorders, patients with iatrogenic immunosuppression, and patients with human immunodeficiency virus infection/AIDS are also highlighted. Recommendations are proposed for the care and monitoring of immunosuppressed patients with melanoma. With better understanding of the molecular microenvironment and clinical course of melanoma in immunosuppressed patients, novel therapies could be developed and outcomes potentially affected in these patients.

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Melanoma Cells Inhibit Natural Killer Cell Function by Modulating the Expression of Activating Receptors and Cytolytic Activity

Cited by 267 publications

References 47 publications

NK cells and cancer: you can teach innate cells new tricks

NK cells and cancer: you can teach innate cells new tricks

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

Melanoma in Immunosuppressed Patients

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