Application of natural killer cells in pancreatic cancer (Review)

Peng, Xiaobo; Chen, Ling; Yuan, Jiao; Wang, Yujie; Hao, Zhibin; Zhan, Xi

doi:10.3892/ol.2021.12908

Cited by 9 publications

(6 citation statements)

References 62 publications

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“…Typically, the number and functionality of DCs and NK cells decreases as PDAC progresses, but the reduction of NK cells begins with the formation of early PanIN lesions. 37,38 Although we have an increase in PanIN-1 lesions, we found no changes in DCs and a significant increase in NK cells with loss of AHR suggesting the increase in pre-cursor lesions is more likely attributed to changes seen in the adaptive immune groups.…”

Section: Macrophages Dendritic Cells Natural Killer Cells B-cells And...mentioning

confidence: 51%

“…In addition to increases in immunosuppressive immune types, there is usually a notable lack of dendritic cells (DCs) and natural killer (NK) cells found in the PDAC microenvironment. 37 The number of DC and NK cells are lowest in the pancreas of patients with a tumor, while exogenously increasing the number of DC or NK cells has been shown to reduce PDAC tumor and PanIN size. 38 However, in this study, we found no changes in DCs (Supplemental Figure 2) and a significant increase in NKs after AHR knockout in KC mice (Figure 4) suggesting the increase in PanIN-1 formation should be attributed to another immune group.…”

Section: Increase In Panin-1 Lesions After Ahr Knockout Is Not Due To...mentioning

confidence: 99%

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Aryl hydrocarbon receptor knockout accelerates PanIN formation and fibro-inflammation in a mutantKras-driven pancreatic cancer model

Walcheck

Schwartz

Carrillo

et al. 2023

Preprint

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Objectives: The pathogenesis of pancreas cancer (PDAC) remains poorly understood, hindering efforts to develop a more effective therapy for PDAC. Recent discoveries show the aryl hydrocarbon receptor (AHR) plays a crucial role in the pathogenesis of several cancers, and can be targeted for therapeutic effect. However, its involvement in PDAC remains unclear. Therefore, we evaluated the role of AHR in the development of PDAC in vivo. Methods: We created a global AHR-null, mutant Kras-driven PDAC mouse model (A-/-KC) and evaluated the changes in PDAC precursor lesion formation (Pan-IN 1, 2, and 3) and associated fibro-inflammation between KC and A-/-KC at 5 months of age. We then examined the changes in the immune microenvironment followed by single-cell RNA-sequencing analysis to evaluate concomitant transcriptomic changes. Results: We found a significant increase in PanIN-1 lesion formation and PanIN-1 associated fibro-inflammatory infiltrate in A-/-KC vs KC mice. This was associated with significant changes in the adaptive immune system, particularly a decrease in the CD4+/CD8+ T-cell ratio, as well as a decrease in the T-regulatory/Th17 T-cell ratio suggesting unregulated inflammation. Conclusion: These findings show the loss of AHR results in heightened Kras-induced PanIN formation, through modulation of immune cells within the pancreatic tumor microenvironment.

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Section: Macrophages Dendritic Cells Natural Killer Cells B-cells And...mentioning

confidence: 51%

Section: Increase In Panin-1 Lesions After Ahr Knockout Is Not Due To...mentioning

confidence: 99%

Aryl hydrocarbon receptor knockout accelerates PanIN formation and fibro-inflammation in a mutantKras-driven pancreatic cancer model

Walcheck

Schwartz

Carrillo

et al. 2023

Preprint

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“…Innate immunity primarily involves two cell types: natural killer (NK) cells and macrophages. NK cells can eliminate tumor or virus-infected cells [40]. In UM, human leukocyte antigen-E (HLA-E), which combines with the inhibitory receptor of NK cells, CD94/NKG2, was found to be overexpressed, resulting in the silencing of the cytolysis procedure mediated by NK cells [39,41].…”

Section: Immune Escape and Immunosuppressive Micro-environment Of Ummentioning

confidence: 99%

Recent Advances and Challenges in Uveal Melanoma Immunotherapy

Xiao

Mao

2022

Cancers

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Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Compared to cutaneous melanoma (CM), which mainly harbors BRAF or NRAS mutations, UM predominantly harbors GNAQ or GNA11 mutations. Although primary UM can be controlled locally, approximately 50% of patients still develop metastases. To date, there have been no standard therapeutic strategies for the prevention or treatment of metastases. Unfortunately, chemotherapy and targeted therapies only induce minimal responses in patients with metastatic UM, with a median survival time of only 4–5 months after metastasis detection. Immunotherapy agents, such as immune checkpoint inhibitors, have achieved pioneering outcomes in CM but have shown limited effects in UM. Researchers have explored several feasible checkpoints to identify options for future therapies. Cancer vaccines have shown little in the way of therapeutic benefit in patients with UM, and there are few ongoing trials providing favorable evidence, but adoptive cell transfer-related therapies seem promising and deserve further investigation. More recently, the immune-mobilizing monoclonal T-cell receptor against the cancer molecule tebentafusp showed impressive antitumor effects. Meanwhile, oncolytic viruses and small molecule inhibitors have also gained ground. This review highlights recent progress in burgeoning treatments and provides innovative insights on feasible strategies for the treatment of UM.

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“…Other trials are investigating the action of combining immunotherapy with other interventions, such as chemotherapy, radiotherapy, anti-angiogenic therapy, and stromal targeting agents ( Table 1 ), for better treatment outcomes. Furthermore, multiple clinical trials are also evaluating the effect of natural killer cells and dendritic cells immunotherapies in the treatment of PCs [ 75 ].…”

Section: Overview Of Pancreatic Cancermentioning

confidence: 99%

Pancreatic Cancer: Challenges and Opportunities in Locoregional Therapies

Bazeed

Day

Garg

2022

Cancers

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Pancreatic cancer (PC) remains the seventh leading cause of cancer-related deaths worldwide and the third in the United States, making it one of the most lethal solid malignancies. Unfortunately, the symptoms of this disease are not very apparent despite an increasing incidence rate. Therefore, at the time of diagnosis, 45% of patients have already developed metastatic tumours. Due to the aggressive nature of the pancreatic tumours, local interventions are required in addition to first-line treatments. Locoregional interventions affect a specific area of the pancreas to minimize local tumour recurrence and reduce the side effects on surrounding healthy tissues. However, compared to the number of new studies on systemic therapy, very little research has been conducted on localised interventions for PC. To address this unbalanced focus and to shed light on the tremendous potentials of locoregional therapies, this work will provide a detailed discussion of various localised treatment strategies. Most importantly, to the best of our knowledge, the aspect of localised drug delivery systems used in PC was unprecedentedly discussed in this work. This review is meant for researchers and clinicians considering utilizing local therapy for the effective treatment of PC, providing a thorough guide on recent advancements in research and clinical trials toward locoregional interventions, together with the authors’ insight into their potential improvements.

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Application of natural killer cells in pancreatic cancer (Review)

Cited by 9 publications

References 62 publications

Aryl hydrocarbon receptor knockout accelerates PanIN formation and fibro-inflammation in a mutantKras-driven pancreatic cancer model

Aryl hydrocarbon receptor knockout accelerates PanIN formation and fibro-inflammation in a mutantKras-driven pancreatic cancer model

Recent Advances and Challenges in Uveal Melanoma Immunotherapy

Pancreatic Cancer: Challenges and Opportunities in Locoregional Therapies

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