Elevated IL18 levels in Nasopharyngeal carcinoma induced PD-1 expression on NK cells in TILS leading to poor prognosis

Liou, Anthony Kian-Fong; Soon, Gwyneth; Tan, Louise; Yang, Peng; Cher, Boon Meng; Goh, Boon Cher; Wang, Shi; Lim, Chwee Ming

doi:10.1016/j.oraloncology.2020.104616

Cited by 22 publications

(20 citation statements)

References 38 publications

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“…PD‐1 has been reported on human NK cells from multiple myeloma, 66 Hodgkin's lymphoma, and diffuse large B cell lymphoma, 67 renal cell carcinoma, 68 nasopharyngeal carcinoma, 69,70 ovarian cancer, 70 and Kaposi's sarcoma 71 as well as post‐transplantation lymphoproliferative disorder (PTLD) 72 . Resting NK cells have intracellular stores of PD‐1 mRNA and protein, even in the absence of surface expression, 73 suggesting that they may express PD‐1 under specific circumstances or in specific tissues.…”

Section: The Role Of Checkpoint Receptors On Nk Cellsmentioning

confidence: 99%

Unraveling exhaustion in adaptive and conventional NK cells

Merino

Kim

Miller

et al. 2020

Journal of Leukocyte Biology

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Immune exhaustion in T cells significantly impacts their ability to control malignancies and infections, and its discovery has led to revolutionary therapies for cancer in the form of checkpoint blockade. NK cells, like T cells, are lymphocytes that recognize virally infected and malignantly transformed cells. However, it remains unclear if NK cells are similarly susceptible to exhaustion. In this review, the aims are to summarize what is currently known and to identify key areas of variability that skew the scientific literature on NK cell exhaustion. A lack of consensus on the defining features of NK cell dysfunctional states such as senescence, suppression, and exhaustion has made a comparison between studies difficult. There are also significant differences in the biology of NK cell subsets with long-lived, adaptive NK cells sharing an epigenetic signature closer to memory CD8 + T cells than to conventional NK cells. Very different checkpoint receptor expression and effector functions have been shown in adaptive versus conventional NK cells chronically exposed to activating signals. Adaptive NK cells develop in individuals with cytomegalovirus (CMV) infection and well over half of the human population worldwide is CMV seropositive by adulthood. Despite this high prevalence, most studies do not account or control for this population. This may contribute to some of the variability reported in the literature on checkpoint receptor expression on NK cells. In this review, the protective role that exhaustion plays in T cells will also be discussed and the evidence for a similar phenomenon in NK cells will be examined.

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Section: The Role Of Checkpoint Receptors On Nk Cellsmentioning

confidence: 99%

Unraveling exhaustion in adaptive and conventional NK cells

Merino

Kim

Miller

et al. 2020

Journal of Leukocyte Biology

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“…[156] PD-1 was found expressed on NK cells present in the tumor-infiltrating immune cells in NPC; PD-1 expression on NK cells was notably induced by IL-18, which was significantly higher in NPC biopsy than in normal nasopharynx. [110] PD-L1 in soluble form can be detected in the plasma of NPC patients; soluble PD-L1 levels in plasma were found to positively correlate with clinical stage and N stage. [157] PD-1, CTLA-4, LAG3 and TIM3 are also expressed in some NK cells, which may dampen their response in the presence of corresponding ligands.…”

Section: B7-h6 Bat3 Unknownmentioning

confidence: 97%

“…These elevated IL-18 levels may enhance functional exhaustion of NK cells in NPC through upregulation of PD-1. [110] Perforin Mutations that impair maturation of perforin is associated with chronic active EBV infection, providing evidence of cell-mediated cytotoxicity in controlling EBV infections [111] BZLF1 EBV proteins expressed during type II latency (eg LMP1, LMP2A/B, vBcl2 and vIL10) can contribute to NK evasion. Latent protein LMP1 can contribute to NK evasion in several ways.…”

Section: B4 Cd27 Cd48 Cd70mentioning

confidence: 99%

“…This NK signatures comprised of a gene expression panel of 13 genes such as genes expressing perforin (PRF1), granulysin (GNLY), NKG2A (KLRC1), NKG2C (KLRC2) and CD94 (KLRD1) [127]. In contrast, another study reported poorer two-year survival in NPC patients with a higher percentage of CD56 + cells, as compared to those with lower CD56 + percentage on immunohistochemistry (IHC) [110]. As this study had examined CD56 as a single parameter due to the limitation of IHC, the use of multi-fluorescence IHC can overcome the difficulty of distinguishing between NK cell versus NKT cell population as well as allowing the evaluation of other surface marker co-expression on NK cells (e.g., CD56 and CD16), so as to better characterize different NK subsets.…”

Section: B7-h6 Bat3 Unknownmentioning

confidence: 99%

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The Role of NK Cells in EBV Infection and EBV-Associated NPC

Png

Yang

Lee

et al. 2021

Viruses

Self Cite

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A vast majority of the population worldwide are asymptomatic carriers of Epstein-Barr Virus (EBV). However, some infected individuals eventually develop EBV-related cancers, including Nasopharyngeal Carcinoma (NPC). NPC is one of the most common EBV-associated epithelial cancers, and is highly prevalent in Southern China and Southeast Asia. While NPC is highly sensitive to radiotherapy and chemotherapy, there is a lack of effective and durable treatment among the 15%–30% of patients who subsequently develop recurrent disease. Natural Killer (NK) cells are natural immune lymphocytes that are innately primed against virus-infected cells and nascent aberrant transformed cells. As EBV is found in both virally infected and cancer cells, it is of interest to examine the NK cells’ role in both EBV infection and EBV-associated NPC. Herein, we review the current understanding of how EBV-infected cells are cleared by NK cells, and how EBV can evade NK cell-mediated elimination in the context of type II latency in NPC. Next, we summarize the current literature about NPC and NK cell biology. Finally, we discuss the translational potential of NK cells in NPC. This information will deepen our understanding of host immune interactions with EBV-associated NPC and facilitate development of more effective NK-mediated therapies for NPC treatment.

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“…High expression of IL-18 has been detected in various cancers, and tumor-derived IL-18 is associated with a poor prognosis (59,60). In NPC, the elevated levels of IL-18 in cancer cells were associated with a high density of tumor infiltrating NK cells and poor overall rates of survival (61). IL-18 had been shown to exert potential immunosuppressive effects in cancer by increasing expression of programmed cell death-1 (PD-1) on activated mature NK cells (59,61).…”

Section: Lmp1 Induction Of Il-18 and Ip-10 Recruit And Suppresses The Amentioning

confidence: 99%

The Role of EBV-Encoded LMP1 in the NPC Tumor Microenvironment: From Function to Therapy

Dawson

Lung

et al. 2021

Front. Oncol.

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Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection. It is also characterized by heavy infiltration with non-malignant leucocytes. The EBV-encoded latent membrane protein 1 (LMP1) is believed to play an important role in NPC pathogenesis by virtue of its ability to activate multiple cell signaling pathways which collectively promote cell proliferation and survival, angiogenesis, invasiveness, and aerobic glycolysis. LMP1 also affects cell-cell interactions, antigen presentation, and cytokine and chemokine production. Here, we discuss how LMP1 modulates local immune responses that contribute to the establishment of the NPC tumor microenvironment. We also discuss strategies for targeting the LMP1 protein as a novel therapy for EBV-driven malignancies.

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Elevated IL18 levels in Nasopharyngeal carcinoma induced PD-1 expression on NK cells in TILS leading to poor prognosis

Cited by 22 publications

References 38 publications

Unraveling exhaustion in adaptive and conventional NK cells

Unraveling exhaustion in adaptive and conventional NK cells

The Role of NK Cells in EBV Infection and EBV-Associated NPC

The Role of EBV-Encoded LMP1 in the NPC Tumor Microenvironment: From Function to Therapy

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