Stromal-like Wilms tumor cells induce human Natural Killer cell degranulation and display immunomodulatory properties towards NK cells

Cantoni, Claudia; Serra, Martina; Parisi, Erica; Azzarone, Bruno; Sementa, Angela Rita; Nasto, Luigi Aurelio; Moretta, Lorenzo; Candiano, Giovanni; Bottino, Cristina; Ghiggeri, Gian Marco; Spaggiari, Grazia Maria

doi:10.1080/2162402x.2021.1879530

Cited by 8 publications

(7 citation statements)

References 47 publications

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“…Recently, it has been suggested that NK cells could play a role in epithelial-to-mesenchymal transition of melanoma cells, favoring their progression to more malignant stages [ 78 ]. Cantoni et al showed that NK cells could efficiently degranulate upon incubation with stromal-like Wilm’s tumor cells whereas, on the other hand, these cells could inhibit NK cells via IDO and PGE2 production [ 79 ]. Finally, TME-associated hypoxia may contribute to partial abrogation of NK cell activity [ 80 , 81 ].…”

Section: Natural Killer Cell Biologymentioning

confidence: 99%

Cord Blood-Derived Natural Killer Cell Exploitation in Immunotherapy Protocols: More Than a Promise?

Damele

Spaggiari

Parodi

et al. 2022

Cancers

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In the last 20 years, Natural Killer (NK) cell-based immunotherapy has become a promising approach to target various types of cancer. Indeed, NK cells play a pivotal role in the first-line defense against tumors through major histocompatibility complex-independent immunosurveillance. Their role in the control of leukemia relapse has been clearly established and, moreover, the presence of NK cells in the tumor microenvironment (TME) generally correlates with good prognosis. However, it has also been observed that, often, NK cells poorly infiltrate the tumor tissue, and, in TME, their functions may be compromised by immunosuppressive factors that contribute to the failure of anti-cancer immune response. Currently, studies are focused on the design of effective strategies to expand NK cells and enhance their cytotoxic activity, exploiting different cell sources, such as peripheral blood (PB), umbilical cord blood (UCB) and NK cell lines. Among them, UCB represents an important source of mature NK cells and CD34+ Hematopoietic Stem and Progenitor Cells (HSPCs), as precursors of NK cells. In this review, we summarize the UCB-derived NK cell activity in the tumor context, review the different in-vitro models to expand NK cells from UCB, and discuss the importance of their exploitation in anti-tumor immunotherapy protocols.

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Section: Natural Killer Cell Biologymentioning

confidence: 99%

Cord Blood-Derived Natural Killer Cell Exploitation in Immunotherapy Protocols: More Than a Promise?

Damele

Spaggiari

Parodi

et al. 2022

Cancers

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“…Up to now, the establishment of primary WT cultures expressing a stable phenotype has been difficult, and few cell lines expressing epithelial characteristics, but not blastemal or mesenchymal morphology, have been obtained [ 74 , 76 , 77 , 78 , 79 ]. Until recently, very few studies from different groups have reported the in vitro stabilization of WT primary cultures displaying mesenchymal [ 80 , 81 ], blastemal, or epithelial features [ 82 , 83 , 84 , 85 ]. Royer Pokora et al stabilized in vitro primary cultures from the stromal component (str-WT), and showed that they bear the same mutations as the primary tumors.…”

Section: From Neuroblastoma To Wilms’ Tumor: the Impact On Nk Cellsmentioning

confidence: 99%

“…str-WT exhibited potent inhibitory effects in vitro on the IL-2-induced proliferation of NK cells and on the expression of the activating receptors NKp30, NKp44, NKG2D, and 2B4. All these inhibitory effects were mediated by tumor-derived indoleamine-2,3-dioxygenase (IDO) metabolites and PGE2 [ 80 ].…”

Section: From Neuroblastoma To Wilms’ Tumor: the Impact On Nk Cellsmentioning

confidence: 99%

Pediatric Tumors-Mediated Inhibitory Effect on NK Cells: The Case of Neuroblastoma and Wilms’ Tumors

Pelosi

Fiore

Matteo

et al. 2021

Cancers

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Natural killer (NK) cells play a key role in the control of cancer development, progression and metastatic dissemination. However, tumor cells develop an array of strategies capable of impairing the activation and function of the immune system, including NK cells. In this context, a major event is represented by the establishment of an immunosuppressive tumor microenvironment (TME) composed of stromal cells, myeloid-derived suppressor cells, tumor-associated macrophages, regulatory T cells and cancer cells themselves. The different immunoregulatory cells infiltrating the TME, through the release of several immunosuppressive molecules or by cell-to-cell interactions, cause an impairment of the recruitment of NK cells and other lymphocytes with effector functions. The different mechanisms by which stromal and tumor cells impair NK cell function have been particularly explored in adult solid tumors and, in less depth, investigated and discussed in a pediatric setting. In this review, we will compare pediatric and adult solid malignancies concerning the respective mechanisms of NK cell inhibition, highlighting novel key data in neuroblastoma and Wilms’ tumor, two of the most frequent pediatric extracranial solid tumors. Indeed, both tumors are characterized by the presence of stromal cells acting through the release of immunosuppressive molecules. In addition, specific tumor cell subsets inhibit NK cell cytotoxic function by cell-to-cell contact mechanisms likely controlled by the transcriptional coactivator TAZ. These findings could lead to a more performant diagnostic approach and to the development of novel immunotherapeutic strategies targeting the identified cellular and molecular targets.

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“…Moreover, MSCs cannot only effectively inhibit IL-2-induced NK cell proliferation but also prevent cytotoxic activity and cytokine production. Notably, indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2) were reported to be the key mediators in MSC-induced inhibition of NK cells [ 73 , 74 ].…”

Section: The Biological Characteristics and Research Status Of Mscsmentioning

confidence: 99%

The Immunomodulatory Properties of Mesenchymal Stem Cells Play a Critical Role in Inducing Immune Tolerance after Liver Transplantation

Cai

Mao

et al. 2021

Stem Cells International

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Although liver transplantation is considered to be the best choice for patients with end-stage liver diseases, postoperative immune rejection still cannot be overlooked. Patients with liver transplantation have to take immunosuppressive drugs for a long time or even their entire lives, in which heavy economic burden and side effects caused by the drugs have become the major impediment for liver transplantation. There is a growing body of evidences indicating that mesenchymal stem cell (MSC) transplantation, a promising tool in regenerative medicine, can be used as an effective way to induce immune tolerance after liver transplantation based on their huge expansion potential and unique immunomodulatory properties. MSCs have been reported to inhibit innate immunity and adaptive immunity to induce a tolerogenic microenvironment. In in vitro studies, transplanted MSCs show plasticity in immune regulation by altering their viability, migration, differentiation, and secretion in the interactions with the surrounding host microenvironment. In this review, we aim to provide an overview of the current understanding of immunomodulatory properties of MSCs in liver transplantation, to elucidate the potential mechanisms behind MSCs regulating immune response, especially in vivo and the influence of the microenvironment, and ultimately to discuss the feasible strategies to improve the clinical prognosis of liver transplantation. Only after exhaustive understanding of potential mechanisms of the MSC immunomodulation can we improve the safety and effectiveness of MSC treatment and achieve better therapeutic effects.

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Stromal-like Wilms tumor cells induce human Natural Killer cell degranulation and display immunomodulatory properties towards NK cells

Cited by 8 publications

References 47 publications

Cord Blood-Derived Natural Killer Cell Exploitation in Immunotherapy Protocols: More Than a Promise?

Cord Blood-Derived Natural Killer Cell Exploitation in Immunotherapy Protocols: More Than a Promise?

Pediatric Tumors-Mediated Inhibitory Effect on NK Cells: The Case of Neuroblastoma and Wilms’ Tumors

The Immunomodulatory Properties of Mesenchymal Stem Cells Play a Critical Role in Inducing Immune Tolerance after Liver Transplantation

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