Fc Receptor is Involved in Nk Cell Functional Anergy Induced by Miapaca2 Tumor Cell Line

Ostapchuk, Yekaterina O.; Perfilyeva, Yuliya V.; Kali, Aikyn; Tleulieva, Raikhan; Yurikova, O.Yu.; Stanbekova, Gulshan; Karal'nik, B V; Belyaev, Nikolai N.

doi:10.1080/08820139.2020.1813757

Cited by 5 publications

(7 citation statements)

References 49 publications

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“…Inhibition of the FGL2 promotes antiviral T-cell and B-cell responses 87 . Recent studies have showed that exogenous FGL2 inhibits the cytotoxicity of NK cells 88 .…”

Section: Targeted Therapy and Immunotherapymentioning

confidence: 99%

The role of Fibrinogen-like proteins in Cancer

Yu¹,

Li²,

Shen³

et al. 2021

Int. J. Biol. Sci.

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Fibrinogen-associated protein (FREP) family is a family of proteins with a fibrin domain at the carboxyl terminus. Recent investigations illustrated that two members of FREP family, fibrinogen-like protein-1 (FGL1) and fibrinogen-like protein-2 (FGL2), play crucial roles in cancer by regulating the proliferation, invasion, and migration of tumor cells, or regulating the functions of immune cells in tumor microenvironment. Meanwhile, they are potential targets for medical intervention of tumor development. In this review, we discussed the structure, and the roles of FGL1 and FGL2 in tumors, especially the roles in regulating immune cell functions.

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“…Inhibition of the FGL2 promotes antiviral T-cell and B-cell responses 87 . Recent studies have showed that exogenous FGL2 inhibits the cytotoxicity of NK cells 88 .…”

Section: Targeted Therapy and Immunotherapymentioning

confidence: 99%

The role of Fibrinogen-like proteins in Cancer

Yu¹,

Li²,

Shen³

et al. 2021

Int. J. Biol. Sci.

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“…We found that the Klrg1 high stage corresponded to a late population to the CD11b SP stage. Itgam is clustered with genes known to enhance NK cell cytotoxic function through a pseudotemporal expression pattern (18)(19)(20), while Klrg1 shows the opposite orientation (21)(22)(23)(24). Furthermore, we found that the transcriptional levels of AP-1 family members were consistently downregulated in Ezh2-deficient NK cells.…”

Section: Introductionmentioning

confidence: 70%

“…Fcgr2b, Fgl2, Cx3cr1, and Klra9 (Ly49C) were grouped into Cluster 6 with Klrg1 (Figure 2). The expression of Fcgr2b, Fgl2, and Ly49C is known to impair the cytotoxic function of NK cells (21)(22)(23). Cx3cr1 + NK cells have been reported to show less proliferation potential than Cx3cr1 -NK cells (30).…”

Section: Maturation Trajectory Of Ezh2 -/-Nk Cells Arresting In Cd11b Sp Stagementioning

confidence: 99%

Single-Cell Sequencing Reveals the Novel Role of Ezh2 in NK Cell Maturation and Function

Su²,

Huang³

et al. 2021

Front. Immunol.

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Natural killer (NK) cells are lymphocytes primarily involved in innate immunity and exhibit important functional properties in antimicrobial and antitumoral responses. Our previous work indicated that the enhancer of zeste homolog 2 (Ezh2) is a negative regulator of early NK cell differentiation and function through trimethylation of histone H3 lysine 27 (H3K27me3). Here, we deleted Ezh2 from immature NK cells and downstream progeny to explore its role in NK cell maturation by single-cell RNA sequencing (scRNA-seq). We identified six distinct NK stages based on the transcriptional signature during NK cell maturation. Conditional deletion of Ezh2 in NK cells resulted in a maturation trajectory toward NK cell arrest in CD11b SP stage 5, which was clustered with genes related to the activating function of NK cells. Mechanistically, we speculated that Ezh2 plays a critical role in NK development by activating AP-1 family gene expression independent of PRC2 function. Our results implied a novel role for the Ezh2-AP-1-Klrg1 axis in altering the NK cell maturation trajectory and NK cell-mediated cytotoxicity.

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“…In addition, tumoral cells are seen to exhibit intricate crosstalk with NK effector cells and have been shown to induce functional deregulation[ 54 ]. Co-culture with the pancreatic cancer cell line MiaPaca2 was found to induce NK cell anergy via fibrinogen-like protein 2 and was characterised through decreased expression of DNAM-1, IFN-γ and CD107a and increased expression of PD-1[ 55 ]. Importantly, when co-cultured, anergic NK cells were seen to induce anergy in naïve NK cells, reducing IFN-γ and CD107a expression[ 55 ].…”

Section: Natural Killer Cellsmentioning

confidence: 99%

“…Co-culture with the pancreatic cancer cell line MiaPaca2 was found to induce NK cell anergy via fibrinogen-like protein 2 and was characterised through decreased expression of DNAM-1, IFN-γ and CD107a and increased expression of PD-1[ 55 ]. Importantly, when co-cultured, anergic NK cells were seen to induce anergy in naïve NK cells, reducing IFN-γ and CD107a expression[ 55 ]. Further work investigating the reversal of NK cell anergy, both tumour-dependent and bystander anergy may lead to novel therapeutic insights, and provide a baseline from which to further challenge PDAC immune evasion.…”

Section: Natural Killer Cellsmentioning

confidence: 99%

Natural killer cells in pancreatic cancer stroma

Fincham¹,

Delvecchio²,

Goulart³

et al. 2021

WJG

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Pancreatic cancer remains one of medicine’s largest areas of unmet need. With five-year survival rates of < 8%, little improvement has been made in the last 50 years. Typically presenting with advance stage disease, treatment options are limited. To date, surgery remains the only potentially curative option, however, with such late disease presentation, the majority of patients are unresectable. Thus, new therapeutic options and a greater understanding of the complex stromal interactions within the tumour microenvironment are sorely needed to revise the dismal outlook for pancreatic cancer patients. Natural killer (NK) cells are crucial effector units in cancer immunosurveillance. Often used as a prognostic biomarker in a range of malignancies, NK cells have received much attention as an attractive target for immunotherapies, both as cell therapy and as a pharmaceutical target. Despite this interest, the role of NK cells in pancreatic cancer remains poorly defined. Nevertheless, increasing evidence of the importance of NK cells in this dismal prognosis disease is beginning to come to light. Here, we review the role of NK cells in pancreatic cancer, examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of NK cells as therapy.

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Fc Receptor is Involved in Nk Cell Functional Anergy Induced by Miapaca2 Tumor Cell Line

Cited by 5 publications

References 49 publications

The role of Fibrinogen-like proteins in Cancer

The role of Fibrinogen-like proteins in Cancer

Single-Cell Sequencing Reveals the Novel Role of Ezh2 in NK Cell Maturation and Function

Natural killer cells in pancreatic cancer stroma

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