Primitive Neuroectodermal Tumor in an Ovarian Cystic Teratoma: Natural Killer and Neuroblastoma Cell Analysis

Tabellini, Giovanna; Benassi, Marzia; Marcenaro, Emanuela; Coltrini, Daniela; Patrizi, Ornella; Ricotta, Doris; Rampinelli, Fabio; Moretta, Alessandro; Parolini, Silvia

doi:10.1159/000357802

Cited by 12 publications

(6 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, in a case of neuroblastoma arising in an ovarian cystic teratoma, B7-H3 was expressed in addition to substantial amounts of HLA class-I molecules, suggesting a protective immune-evasive mechanism by neuroblastoma cells against NK cell-mediated lysis. Additionally, receptors such as DNAM-1 (CD226) and CD16 were expressed with lower intensity on NK cells isolated from peritoneal fluid of these patients in comparison to NK cells from the peripheral blood (363). Bispecific killer cell engager (BiKE) treatment, one of the two forms of antibody therapeutics, was demonstrated to significantly inhibit cell growth by inducing natural killer cells when exploring B7-H3 as a potential target in NSCLC (364).…”

Section: B7-h3mentioning

confidence: 99%

NK Cell-Based Immune Checkpoint Inhibition

Arooj²,

2020

View full text Add to dashboard Cite

Immunotherapy, with an increasing number of therapeutic dimensions, is becoming an important mode of treatment for cancer patients. The inhibition of immune checkpoints, which are the source of immune escape for various cancers, is one such immunotherapeutic dimension. It has mainly been aimed at T cells in the past, but NK cells are a newly emerging target. Simultaneously, the number of checkpoints identified has been increasing in recent times. In addition to the classical NK cell receptors KIRs, LIRs, and NKG2A, several other immune checkpoints have also been shown to cause dysfunction of NK cells in various cancers and chronic infections. These checkpoints include the revolutionized CTLA-4, PD-1, and recently identified B7-H3, as well as LAG-3, TIGIT & CD96, TIM-3, and the most recently acknowledged checkpoint-members of the Siglecs family (Siglec-7/9), CD200 and CD47. An interesting dimension of immune checkpoints is their candidacy for dual-checkpoint inhibition, resulting in therapeutic synergism. Furthermore, the combination of immune checkpoint inhibition with other NK cell cytotoxicity restoration strategies could also strengthen its efficacy as an antitumor therapy. Here, we have undertaken a comprehensive review of the literature to date regarding NK cell-based immune checkpoints.

show abstract

Section: B7-h3mentioning

confidence: 99%

NK Cell-Based Immune Checkpoint Inhibition

Arooj²,

2020

View full text Add to dashboard Cite

show abstract

“…PD-1 + NK cells are thought to be memory-like NK cells ( 64 ) or functionally exhausted, given their impaired cytotoxicity and cytokine production ( 65 , 66 ). PD-1 is upregulated on NK cells from ascites of ovarian cancer patients and on peripheral blood NK cells from Kaposi sarcoma patients, which suggests impaired NK cell function ( 66 , 67 ). Treatment with an anti-PD-1 antibody increases NK cell cytotoxicity against autologous MM cells in vitro ( 68 ).…”

Section: Immune Checkpoint Receptorsmentioning

confidence: 99%

Targeting Checkpoint Receptors and Molecules for Therapeutic Modulation of Natural Killer Cells

Kim

2018

Front. Immunol.

View full text Add to dashboard Cite

Among the most promising therapeutic modalities for cancer treatment is the blockade of immune checkpoint pathways, which are frequently co-opted by tumors as a major mechanism of immune escape. CTLA-4 and PD-1 are the representative examples, and their blockade by therapeutic antibodies leads to enhanced anti-tumor immunity with durable clinical responses, but only in a minority of patients. This has highlighted the need to identify and target additional immune checkpoints that can be exploited to further enhance immune responses to refractory cancers. These emerging targets include natural killer (NK) cell-directed checkpoint receptors (KIR and CD94/NKG2A) as well as the NK- and T cell-expressed checkpoints TIM-3, TIGIT, CD96, and LAG-3. Interestingly, the potentiation of anti-tumor immunity by checkpoint blockade relies not only on T cells but also on other components of the innate immune system, including NK cells. NK cells are innate lymphoid cells that efficiently kill tumor cells without MHC specificity, which is complementary to the MHC-restricted tumor lysis mediated by cytotoxic T cells. However, the role of these immune checkpoints in modulating the function of NK cells remains unclear and somewhat controversial. Unraveling the mechanisms by which these immune checkpoints function in NK cells and other immune cells will pave the way to developing new therapeutic strategies to optimize anti-tumor immunity while limiting cancer immune escape. Here, we focus on recent findings regarding the roles of immune checkpoints in regulating NK cell function and their potential application in cancer immunotherapy.

show abstract

“…Remarkably, PD-1 + NK cells are present in higher proportions in the ascites of ovarian-carcinoma patients ( 71 ), suggesting their possible induction/enrichment in tumor microenvironment. Also, in this case, the PD-1 + NK cell subset of these patients displayed a functional defect against PD-L1/PD-L2 + tumor targets.…”

Section: Human Resting Nk Cells Can Express High Levels Of Pd-1 Recepmentioning

confidence: 99%

Features of Memory-Like and PD-1+ Human NK Cell Subsets

et al. 2016

Self Cite

View full text Add to dashboard Cite

Human NK cells are distinguished into CD56brightCD16− cells and CD56dimCD16+ cells. These two subsets are conventionally associated with differential functional outcomes and are heterogeneous with respect to the expression of KIR and CD94/NKG2 heterodimers that represent the two major types of HLA-class I-specific receptors. Recent studies indicated that immature CD56bright NK cells, homogeneously expressing the inhibitory CD94/NKG2A receptor, are precursors of CD56dim NK cells that, in turn, during their process of differentiation, lose expression of CD94/NKG2A and subsequentially acquire inhibitory KIRs and LIR-1. The terminally differentiated phenotype of CD56dim cells is marked by the expression of the CD57 molecule that is associated with poor responsiveness to cytokine stimulation, but retained cytolytic capacity. Remarkably, this NKG2A−KIR+LIR-1+CD57+CD56dim NK cell subset when derived from individuals previously exposed to pathogens, such as human cytomegalovirus (HCMV), may contain “memory-like” NK cells. These cells are generally characterized by an upregulation of the activating receptor CD94/NKG2C and a downregulation of the inhibitory receptor Siglec-7. The “memory-like” NK cells are persistent over time and display some hallmarks of adaptive immunity, i.e., clonal expansion, more effective antitumor and antiviral immune responses, longevity, as well as given epigenetic modifications. Interestingly, unknown cofactors associated with HCMV infection may induce the onset of a recently identified fully mature NK cell subset, characterized by marked downregulation of the activating receptors NKp30 and NKp46 and by the unexpected expression of the inhibitory PD-1 receptor. This phenotype correlates with an impaired antitumor NK cell activity that can be partially restored by antibody-mediated disruption of PD-1/PD-L interaction.

show abstract

Primitive Neuroectodermal Tumor in an Ovarian Cystic Teratoma: Natural Killer and Neuroblastoma Cell Analysis

Cited by 12 publications

References 14 publications

NK Cell-Based Immune Checkpoint Inhibition

NK Cell-Based Immune Checkpoint Inhibition

Targeting Checkpoint Receptors and Molecules for Therapeutic Modulation of Natural Killer Cells

Features of Memory-Like and PD-1+ Human NK Cell Subsets

Contact Info

Product

Resources

About