NK Cell Dysfunction and Checkpoint Immunotherapy

Bi, Jiacheng; Tian, Zhigang

doi:10.3389/fimmu.2019.01999

Cited by 112 publications

(101 citation statements)

References 126 publications

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“…Killer immunoglobulin‐like receptors have been known to regulate NK‐cell activation 114 . The inhibition of killer immunoglobulin‐like receptors has demonstrated an increase in NK activity with a trend towards an increase in response rates when combined with PD‐1 inhibition in head and neck cancer patients (NCT101714739) 115 . For the future, knowledge of how these drugs might benefit patients and which specific patient populations, both alone and in combination with other ICIs, will be important.…”

Section: Discussionmentioning

confidence: 99%

Evolving insights into the mechanisms of toxicity associated with immune checkpoint inhibitor therapy

Mangan

McAlister

Balko

et al. 2020

Brit J Clinical Pharma

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Immune checkpoint inhibitors have emerged as a revolutionary treatment option for patients with various types of malignancy. Although these agents afford a significant improvement in outcomes for melanoma and other previously untreatable malignancies, their novel mechanism of action may predispose patients to immune‐related adverse effects (irAEs). In the tumour neoantigen environment, these irAEs are due to the activation of the immune system by the blockade of suppressive checkpoints, leading to increases in T‐cell activation and proliferation. IrAEs have been reported in almost any organ and at any point in time, even months to years after discontinuation of therapy. Certain populations with distinct physiological changes, genetic risk factors, and specific antigen exposures may be more highly predisposed to develop irAEs. This review discusses the incidence and mechanisms of irAEs and the relationship between host factors and irAE occurrence.

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Section: Discussionmentioning

confidence: 99%

Evolving insights into the mechanisms of toxicity associated with immune checkpoint inhibitor therapy

Mangan

McAlister

Balko

et al. 2020

Brit J Clinical Pharma

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“…They are enriched in mucosal tissues, including the intestinal tract (37) and respond to signals derived from their micro-environment such as cytokines, alarmins, and other inflammatory and non-inflammatory stimuli (38,39) to drive appropriate immune responses and maintain tissue homeostasis. In addition, ILCs express particular receptors and ligands at their surface regulating further their function (40,41). NK cells and ILC1 are mainly involved in the early protection against viruses (42), bacteria (43,44), and cancer (45) through the secretion of interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (46).…”

Section: The Tumor Immune Contexture In Colorectal Cancer-the Successmentioning

confidence: 99%

“…If so, similar NK cell-ILC1 transdifferentiation could occur in CRC tumors and this would potentially with worsen prognosis. Collectively, it is clear that NK cells are involved in the control of CRC progression and metastasis but are also susceptible to tumor-directed dysregulation (41). To circumvent such events, current NK cell-based therapies are designed to boost NK cell functions in an effort to strategically further improve patient outcomes (68)(69)(70)(71).…”

Section: Type 1 Innate Lymphoid Cellsmentioning

confidence: 99%

Innate Lymphoid Cells in Colorectal Cancers: A Double-Edged Sword

et al. 2020

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The immune system plays a fundamental role at mucosal barriers in maintaining tissue homeostasis. This is particularly true for the gut where cells are flooded with microbial-derived signals and antigens, which constantly challenge the integrity of the intestinal barrier. Multiple immune cell populations equipped with both pro-and anti-inflammatory functions reside in the gut tissue and these cells tightly regulate intestinal health and functions. Dysregulation of this finely tuned system can progressively lead to autoimmune disease and inflammation-driven carcinogenesis. Over the last decade, the contribution of the adaptive immune system in controlling colorectal cancer has been studied in detail, but the role of the innate system, particularly innate lymphoid cells (ILCs), have been largely overlooked. By sensing their microenvironment, ILCs are essential in supporting gut epithelium repair and controling bacterial-and helminth-mediated intestinal infections, highlighting their important role in maintaining tissue integrity. Accumulating evidence also suggests that they may play an important role in carcinogenesis including intestinal cancers. In this review, we will explore the current knowledge about the pro-and anti-tumor functions of ILCs in colorectal cancer.

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“…Inhibitory receptors have a critical role in regulating immune responses to infections, thereby limiting autoimmunity and/or immunopathology ( Bi and Tian, 2019 ; Joller and Kuchroo, 2017 ). However, increased and sustained expression of inhibitory receptors, often found in patients with chronic viral infections and malignancies, is a principle mechanism priming lymphocytes to be dysfunctional.…”

Section: Introductionmentioning

confidence: 99%

“…However, increased and sustained expression of inhibitory receptors, often found in patients with chronic viral infections and malignancies, is a principle mechanism priming lymphocytes to be dysfunctional. The suppressive role of some inhibitory receptors, programmed cell death protein 1 (PD-1), cytotoxic T lymphocyte-associated protein 4 (CTLA-4), lymphocyte activation gene 3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), and, more recently, T cell immunoglobulin and ITIM domain (TIGIT), is relatively well understood ( Bi and Tian, 2019 ; Golden-Mason and Rosen, 2013 ; Joller and Kuchroo, 2017 ; Lee et al, 2010 ). With chronic antigen availability, the surface expression of the inhibitory receptor is significantly upregulated and maintained on T and NK cells ( Bi and Tian, 2019 ; Joller and Kuchroo, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Expression of Inhibitory Receptors on T and NK Cells Defines Immunological Phenotypes of HCV Patients with Advanced Liver Fibrosis

Okwor

Crawley

et al. 2020

iScience

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Summary Chronic HCV can result in advanced liver disease, including cirrhosis. Patients with advanced fibrosis experience poor clinical outcomes and increased risk for hepatocellular carcinoma (HCC). These outcomes are, in part, a consequence of immune dysfunction. Increased inhibitory receptor and Galectin-9 (GAL-9) expression is a possible mechanism promoting lymphocyte dysfunction. In this study, we measured the expression of inhibitory receptors and GAL-9 on T/NK cells of patients with chronic HCV with no to moderate fibrosis (F0-F2) and advanced fibrosis (F3-F4). To analyze their co-expression, we employed t-SNE analysis. Notably, we found that F3-F4 patients had higher frequencies of >3 inhibitory receptor co-expression on NK cells. Moreover, F3-F4 patients manifest a higher frequency of NK cells co-expressing TIGIT and TIM-3, and CD4/NK cells co-expressing LAG-3 and GAL-9. In conclusion, we identified phenotypes of immune dysregulation that could explain the increased susceptibility to infection and HCC in patients with chronic HCV with advanced fibrosis.

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NK Cell Dysfunction and Checkpoint Immunotherapy

Cited by 112 publications

References 126 publications

Evolving insights into the mechanisms of toxicity associated with immune checkpoint inhibitor therapy

Evolving insights into the mechanisms of toxicity associated with immune checkpoint inhibitor therapy

Innate Lymphoid Cells in Colorectal Cancers: A Double-Edged Sword

Expression of Inhibitory Receptors on T and NK Cells Defines Immunological Phenotypes of HCV Patients with Advanced Liver Fibrosis

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