Progressive natural killer cell dysfunction associated with alterations in subset proportions and receptor expression in soft-tissue sarcoma patients

Bücklein, Veit; Adunka, Tina; Mendler, Anna N.; Issels, Rolf D.; Subklewe, Marion; Schmollinger, Jan C.; Noeßner, Elfriede

doi:10.1080/2162402x.2016.1178421

Cited by 17 publications

(18 citation statements)

References 71 publications

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“…Thus, the NK cells of this patient were obviously inactive or exhausted at this stage of disease. This is consistent with our previous results in chemo-pretreated patients with high-risk soft tissue sarcoma who showed downregulation of NKG2D-expressing NK cells accompanied with decreased cytotoxic activity [25]. Treatment with regional hyperthermia may have functionally activated patient NK cells and CD56 bright NK cells, which increased continuously with each treatment cycle.…”

Section: Discussionsupporting

confidence: 92%

Systemic antitumor effect by regional hyperthermia combined with low-dose chemotherapy and immunologic correlates in an adolescent patient with rhabdomyosarcoma – a case report

Issels¹,

Линднер²,

Bergwelt‐Baildon³

et al. 2020

International Journal of Hyperthermia

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Introduction: An abscopal effect is a clinical observation whereby a local treatment is associated with regression of metastatic cancer at a site distant from the primary location of treatment. Here, we describe the clinical systemic effect induced by regional hyperthermia combined with low-dose chemotherapy and provide immunologic correlates. Case presentation: A 15-year-old patient had been diagnosed with alveolar rhabdomyosarcoma (ARMS). All previous treatment options failed in the patient including haploidentical stem cell transplantation and donor lymphocyte infusion. The patient presented with local and metastatic disease, and upon admission, underwent regional hyperthermia combined with low-dose chemotherapy. Immediately following therapy severe skin reactions were observed. Skin biopsies revealed an intraepithelial lymphocytic infiltration dominated by CD3 þ /CD8 þ T cells with a regular network of dendritic cells. Clinical images compared before and during sequential treatment cycles showed complete metabolic response of the local tumor for more than 10 months of therapy. In addition, metastases completely regressed although they were not direct targets of regional hyperthermia. The systemic effect was associated with enhanced frequency of NK cells and T cells expressing the lectin-like natural-killer group 2 D activating receptor (NKG2D), an increase of the CD56 bright subset of NK cells, as well as an increase of effector/memory and effector CD8 þ and CD4 þ T cells in the blood while the percentage of CD25 þ FOXP3 þ regulatory T cells declined. Conclusions: Regional hyperthermia combined with low-dose chemotherapy had the potential to create a systemic effect which was associated with activation of NK cells and T cells.

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Section: Discussionsupporting

confidence: 92%

Systemic antitumor effect by regional hyperthermia combined with low-dose chemotherapy and immunologic correlates in an adolescent patient with rhabdomyosarcoma – a case report

Issels¹,

Линднер²,

Bergwelt‐Baildon³

et al. 2020

International Journal of Hyperthermia

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“…Similar to SARS-CoV-2 infection in patients, decreased NK cell function in the tumor microenvironment, and peripheral blood of cancer patients as well as down-modulation of CD16 receptors on the surface of NK cells have been reported previously (23,(35)(36)(37)(38)(39)(40). Decreased function of NK cells is associated with increased viral infection and cancer risk, whereas higher function was correlated with prevention of establishment and progression of infection and cancer (16)(17)(18)(19).…”

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confidence: 59%

The Potential Effect of Novel Coronavirus SARS-CoV-2 on NK Cells; A Perspective on Potential Therapeutic Interventions

Jewett¹

2020

Front. Immunol.

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Coronavirus-induced disease-2019 (COVID-19) continues to cause significant morbidity and mortality worldwide. While studies on SARS-CoV-2 effects on immune cell function continue to progress, we know very little about the significance of depletion of key immune effectors by the virus in the mortality and morbidity of the disease. This commentary outlines what is the reported literature thus far on the effect of virus on NK cells known to kill virally infected cells. It also underscores the necessity for the future comprehensive studies of NK cells in SARS-CoV-2 infected individuals and animal models to better understand the role and significance of reported NK cell depletion and functional inactivation in disease morbidity and mortality, in hope to design effective therapeutic interventions for the disease.

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“…Dysfunction of NK cells, including decreased cell number and defects in cytotoxicity, has been reported in many solid tumors. 22 , 23 Indeed, various strategies aimed at rescuing NK-cell dysfunction or enhance NK-cell cytotoxicity have been reported and have displayed great potential in tumor therapy. 21 Our data here strongly suggested PD-1 as a potential target to rescue NK-cell dysfunction in tumor therapy.…”

Section: Discussionmentioning

confidence: 99%

“… 21 However, tumor-induced unbalanced expression of activating/inhibitory receptors hampers NK cell-mediated immune surveillance and promotes tumor progression. As a result, people with advanced cancer often process dysfunctional NK cells, 22 and rescuing the function of NK cells in cancer immunotherapy has been attracting substantial attention. 23 , 24 …”

Section: Introductionmentioning

confidence: 99%

Increased expression of programmed cell death protein 1 on NK cells inhibits NK-cell-mediated anti-tumor function and indicates poor prognosis in digestive cancers

et al. 2017

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Abnormal expression of activating/inhibitory receptors leads to natural killer (NK) cells dysfunction in tumor. Here we show that programmed cell death protein 1 (PD-1), a well-known immune checkpoint of T cells, is highly expressed on peripheral and tumor-infiltrating NK cells from patients with digestive cancers including esophageal, liver, colorectal, gastric and biliary cancer. The increased PD-1 expression on NK cells indicates poorer survival in esophageal and liver cancers. Blocking PD-1/PD-L1 signaling markedly enhances cytokines production and degranulation and suppresses apoptosis of NK cells in vitro. PD-1/PD-L1 exerts inhibitory effect through repressing the activation of PI3K/AKT signaling in NK cells. More importantly, a PD-1 blocking antibody was found to significantly suppress the growth of xenografts in nude mice, and this inhibition of tumor growth was completely abrogated by NK depletion. These findings strongly suggested that PD-1 is an inhibitory regulator of NK cells in digestive cancers. PD-1 blockade might be an efficient strategy in NK cell-based tumor immunotherapy.

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Progressive natural killer cell dysfunction associated with alterations in subset proportions and receptor expression in soft-tissue sarcoma patients

Cited by 17 publications

References 71 publications

Systemic antitumor effect by regional hyperthermia combined with low-dose chemotherapy and immunologic correlates in an adolescent patient with rhabdomyosarcoma – a case report

Systemic antitumor effect by regional hyperthermia combined with low-dose chemotherapy and immunologic correlates in an adolescent patient with rhabdomyosarcoma – a case report

The Potential Effect of Novel Coronavirus SARS-CoV-2 on NK Cells; A Perspective on Potential Therapeutic Interventions

Increased expression of programmed cell death protein 1 on NK cells inhibits NK-cell-mediated anti-tumor function and indicates poor prognosis in digestive cancers

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