The activating receptor NKG2D (natural-killer group 2, member D) and its ligands play an important role in the NK, gammadelta(+) and CD8(+) T-cell-mediated immune response to tumors. Ligands for NKG2D are rarely detectable on the surface of healthy cells and tissues, but are frequently expressed by tumor cell lines and in tumor tissues. It is evident that the expression levels of these ligands on target cells have to be tightly regulated to allow immune cell activation against tumors, but at the same time avoid destruction of healthy tissues. Importantly, it was recently discovered that another safeguard mechanism controlling activation via the receptor NKG2D exists. It was shown that NKG2D signaling is coupled to the IL-15 receptor pathway in a cell-specific manner suggesting that priming of NKG2D-mediated activation depends on the cellular microenvironment and the distinct cellular context. This review will provide a broad overview of our up-to-date knowledge of the NKG2D receptor and its ligands in the context of tumor immunology. Strategies to amplify NKG2D-mediated antitumor responses and counteract tumor immune escape mechanisms will be discussed.

NKG2D ligands in tumor immunity

Objectives To investigate the potential association between tumour necrosis factor (TNF) inhibitor treatment and malignant melanomas in rheumatoid arthritis, melanoma risks in rheumatoid arthritis patients not treated with biological drugs, and risk of all site cancer with TNF inhibitors as used in rheumatoid arthritis. Design Population based cohort study. Setting Prospectively recorded data from national clinical, health, and demographic registers in Sweden 2001-10. Patients with rheumatoid arthritis treated (n=10 878) or not (n=42 198) with TNF inhibitors and matched general population comparators (n=162 743). Main outcome measures The primary outcome was first invasive melanoma in people without any history of invasive cancer of any type. Hazard ratios were estimated using Cox regression, comparing non-biological drug treated rheumatoid arthritis patients with the general population comparator and TNF inhibitor treated rheumatoid arthritis patients with those not treated with biological drugs. Secondary outcomes included in situ melanomas, second primary melanomas, and all site cancer. Results 113 first invasive melanomas occurred in rheumatoid arthritis patients not treated with biological drugs, and 393 occurred in the general population comparator cohort. Rheumatoid arthritis patients not treated with biological drugs were not at significantly increased risk of melanoma compared with the general population (hazard ratio 1.2, 95% confidence interval 0.9 to 1.5). 38 first invasive melanomas occurred in rheumatoid arthritis patients treated with TNF inhibitors; these patients had an increased risk of melanoma compared with rheumatoid arthritis patients not treated with biological drugs (hazard ratio 1.5, 1.0 to 2.2; 20 additional cases per 100 000 person years). The risk of a second primary melanoma was non-significantly increased (hazard ratio 3.2, 0.8 to 13.1; n=3 v 10) in rheumatoid arthritis patients treated with TNF inhibitors compared with those not treated with biological drugs. Conclusion Overall, patients with rheumatoid arthritis who have not been treated with biological drugs are not at increased risk of invasive melanoma compared with the general population. Rheumatoid arthritis patients selected for TNF inhibitor treatment are not at increased overall risk for cancer but have a 50% increased relative risk of invasive melanoma. Given the small increase in absolute risk, these finding may not markedly shift the overall risk-benefit balance of TNF inhibitors as used in clinical practice but might do so in patients at high risk of melanoma for other reasons.

https://www.bmj.com/content/bmj/346/bmj.f1939.full.pdf

Rheumatoid arthritis, anti-tumour necrosis factor therapy, and risk of malignant melanoma: nationwide population based prospective cohort study from Sweden.

Primary melanoma of the urogenital tract in women is rare, but biologically aggressive. They usually affect elderly women and account for less than 10% of all cancer of the urogenital tract in women and less than 10% of all melanoma diagnosed in women. Tumours originate from melanocytes that are present in the urogenital mucosal epithelium of about 3% of women. Tumour staging can be challenging; however, the American Joint Committee on Cancer melanoma staging system has been recommended for use in vulvar and vaginal melanoma. Surgery is the treatment of choice; less-extensive surgery can be a sensible approach because satisfactory locoregional control might be obtained from wide local excision and radiotherapy, without the morbidity and disfigurement associated with radical surgery. Complete regional lymphadenectomy does not seem necessary if a sentinel lymph-node biopsy sample is negative; however, this decision should be made with caution. Various chemotherapy and biotherapy (ie, immunotherapy and biological-response modifiers) regimens have been used in advanced or metastatic melanoma. However, the role of chemotherapy for women with urogenital-tract melanoma has not been established, and biotherapy methods presented to date have been anecdotal.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(08)70254-7.pdf

Management of primary melanoma of the female urogenital tract

Melanoma Induces Immunosuppression by Up-Regulating FOXP3+ Regulatory T Cells

Topical interferon alfa in the treatment of conjunctival melanoma and primary acquired melanosis complex.

Melanoma continues to be one of the most difficult to treat of all solid tumors. Many new advances have been made in the surgical management of melanoma, including new guidelines for margins of excision, as well as sentinel node biopsy for the diagnosis of lymph node micrometastases. The search continues for an effective adjuvant melanoma treatment that can prevent local and distant recurrences. Melanoma is one of the most immunogenic of all tumors, and several clinical trials testing the immunotherapy of melanoma have been conducted, including trials in interferon, interleukin-2, and melanoma vaccines. Here we discuss many of the recent clinical trials in the surgical management of melanoma, in addition to the advances that have been made in the field of immunotherapy. A new second-generation melanoma vaccine, DC-MelVac (patent # 11221/5), has recently been granted FDA approval for Phase I clinical trials and will be introduced in this review.

The treatment of melanoma with an emphasis on immunotherapeutic strategies.

Dendritic cells (DCs) possess the unique abilities to initiate a primary immune response and to present antigens to naive T lymphocytes. Recently, there has been a rapidly growing interest in the use of DCs in active specific immunotherapy (ASI) for the treatment of patients with cancer. In the present study, we determined the ability of DCs to express Melanoma-Associated Antigens (MAAs) from a polyvalent Melanoma Vaccine (DC-MelVac; Patent# 11221/5) developed in our facility. The vaccine consists of a recombinant IL-2 gene-encoded vaccinia melanoma oncolysate (rIL-2VMO) derived from an established human melanoma cell line. Our results show that r-IL2VMO-pulsed DCs express MAAs presented by the Mel-2 melanoma cell line oncolysate used in this study. We believe that these promising results will prove useful as an active specific immunotherapeutic agent for patients with Stage III melanoma.

Expression of melanoma-associated antigens in human dendritic cells pulsed with an interleukin-2 gene encoded vaccinia melanoma oncolysate (rIL-2VMO).

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Christopher Boyes

Author Tools

Chat about Author

Papers

The treatment of melanoma with an emphasis on immunotherapeutic strategies.

Expression of melanoma-associated antigens in human dendritic cells pulsed with an interleukin-2 gene encoded vaccinia melanoma oncolysate (rIL-2VMO).