Functional Significance of CD57 Expression on Human NK Cells and Relevance to Disease

Nielsen, Carolyn M.; White, Matthew; Goodier, Martin R.; Riley, Eleanor M.

doi:10.3389/fimmu.2013.00422

Cited by 234 publications

(230 citation statements)

References 122 publications

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“…47%, p = 0.0014; Figure 4C) which have been correlated with memory-like phenotype and are associated in several studies with better outcomes and improved long-term survival across many tumor types. (reviewed in 35 ) Anti-PD-L1 treated animals had very few PD-1 positive NK cells (median 2.9%, range 2.5–4.5%) and also significantly lower frequencies of PD-1 positive T cells (11% vs . 5%, p = 0.0006) (Figure 4D and E).…”

Section: Resultsmentioning

confidence: 99%

PD-L1 blockade enhances anti-tumor efficacy of NK cells

2018

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Anti-PD-1/anti-PD-L1 therapies have shown success in cancer treatment but responses are limited to ~ 15% of patients with lymphocyte infiltrated, PD-L1 positive tumors. Hence, strategies that increase PD-L1 expression and tumor infiltration should make more patients eligible for PD-1/PD-L1 blockade therapy, thus improving overall outcomes. PD-L1 expression on tumors is induced by IFNγ, a cytokine secreted by NK cells. Therefore, we tested if PM21-particle expanded NK cells (PM21-NK cells) induced expression of PD-L1 on tumors and if anti-PD-L1 treatment enhanced NK cell anti-tumor efficacy in an ovarian cancer model. Studies here showed that PM21-NK cells secrete high amounts of IFNγ and that adoptively transferred PM21-NK cells induce PD-L1 expression on SKOV-3 cells in vivo. The induction of PD-L1 expression on SKOV-3 cells coincided with the presence of regulatory T cells (Tregs) in the abdominal cavity and within tumors. In in vitro experiments, anti-PD-L1 treatment had no direct effect on cytotoxicity or cytokine secretion by predominantly PD-1 negative PM21-NK cells in response to PD-L1+ targets. However, significant improvement of NK cell anti-tumor efficacy was observed in vivo when combined with anti-PD-L1. PD-L1 blockade also resulted in increased in vivo NK cell persistence and retention of their cytotoxic phenotype. These results support the use of anti-PD-L1 in combination with NK cell therapy regardless of initial tumor PD-L1 status and indicate that NK cell therapy would likely augment the applicability of anti-PD-L1 treatment.

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Section: Resultsmentioning

confidence: 99%

PD-L1 blockade enhances anti-tumor efficacy of NK cells

2018

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“…These NK cells are functionally different than traditional, CD56 + NK cells-they are terminally differentiated and have higher cytolytic capabilities, and generally act as innate immune regulators despite being less responsive to cytokines and connected to autoimmunity and immunodeficiency (Lopez-Verges et al, 2010;Nielsen et al, 2013). Siniscalco et al (2016) examined 104 children with ASD, and found significantly lower, atypical levels of CD57 + NK cells as compared with both age-matched and adult controls.…”

Section: Immune Dysregulationmentioning

confidence: 99%

The Role of the Immune System in Autism Spectrum Disorder

Meltzer

Water

2016

Neuropsychopharmacol

405

293

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Autism is a neurodevelopmental disorder characterized by deficits in communication and social skills as well as repetitive and stereotypical behaviors. While much effort has focused on the identification of genes associated with autism, research emerging within the past two decades suggests that immune dysfunction is a viable risk factor contributing to the neurodevelopmental deficits observed in autism spectrum disorders (ASD). Further, it is the heterogeneity within this disorder that has brought to light much of the current thinking regarding the subphenotypes within ASD and how the immune system is associated with these distinctions. This review will focus on the two main axes of immune involvement in ASD, namely dysfunction in the prenatal and postnatal periods. During gestation, prenatal insults including maternal infection and subsequent immunological activation may increase the risk of autism in the child. Similarly, the presence of maternally derived anti-brain autoantibodies found in~20% of mothers whose children are at risk for developing autism has defined an additional subphenotype of ASD. The postnatal environment, on the other hand, is characterized by related but distinct profiles of immune dysregulation, inflammation, and endogenous autoantibodies that all persist within the affected individual. Further definition of the role of immune dysregulation in ASD thus necessitates a deeper understanding of the interaction between both maternal and child immune systems, and the role they have in diagnosis and treatment.

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“…49 T cells are not considered to express CD57 at birth; CD57 expression increases with age and is found in 20-30% of young adults and 50-60% of the elderly (above 80 years old). 27 Levels of CD4 C , CD8 C , and CD57 C cells are also frequently increased in many cancers. 26,27,50 Expanded subsets of T cells expressing CD57 but not CD28 were highly associated with survival in our GBM patient cohort.…”

Section: Discussionmentioning

confidence: 99%

“…27 Levels of CD4 C , CD8 C , and CD57 C cells are also frequently increased in many cancers. 26,27,50 Expanded subsets of T cells expressing CD57 but not CD28 were highly associated with survival in our GBM patient cohort. All these patients were HCMV positive, as this was an inclusion criterion for the study.…”

Section: Discussionmentioning

confidence: 99%

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Poor survival in glioblastoma patients is associated with early signs of immunosenescence in the CD4 T-cell compartment after surgery

et al. 2015

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$These authors share senior authorship.Keywords: cytomegalovirus, glioblastoma, immunosenescence, survival, T cells Abbreviations: GBM, glioblastoma multiforme; HCMV, human cytomegalovirus; PBMC, peripheral blood mononuclear cell; Valcyte, valganciclovir; WBC, white blood cell countPatients with glioblastoma multiforme (GBM) are immunosuppressed and have a broad range of immunological defects in both innate and adaptive immune responses. GBMs are frequently infected with human cytomegalovirus (HCMV), a virus capable of causing immunosuppression. In 42 HCMV-positive GBM patients in a clinical trial (VIGAS), we investigated T-cell phenotypes in the blood and assessed their relation to survival. Blood was collected before and 3, 12, and 24 weeks after surgery, and the frequency of T-cell subsets was compared with that in 26 age-matched healthy controls. GBM patients had lower levels of CD3 cells than the controls, but had significantly higher levels of CD4 C CD28 ¡ T cells before and 3 and 12 weeks after surgery and increased levels of CD4 C CD57 C and CD4 C CD57 C CD28 C T cells at all-time points. These T-cell subsets were associated with both immunosenescence and HCMV infection. GBM patients also had higher levels of gd T cells at all-times after surgery and lower levels of CD4 C CD25 C cells before and 3 weeks after surgery than healthy controls. Overall survival was significantly shorter in patients with higher levels of CD4 C CD28 ¡ T cells (p D 0.025), CD4 C CD57 C T (p D 0.025) cells, and CD4 C CD28 ¡ CD57 C CD28 ¡ T cells (p < 0.0004) at 3 weeks after surgery. Our findings indicate that signs of immunosenescence in the CD4 C compartment are associated with poor prognosis in patients with HCMV-positive GBMs and may reflect the HCMV activity in their tumors.

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Functional Significance of CD57 Expression on Human NK Cells and Relevance to Disease

Cited by 234 publications

References 122 publications

PD-L1 blockade enhances anti-tumor efficacy of NK cells

PD-L1 blockade enhances anti-tumor efficacy of NK cells

The Role of the Immune System in Autism Spectrum Disorder

Poor survival in glioblastoma patients is associated with early signs of immunosenescence in the CD4 T-cell compartment after surgery

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