Enhancing Natural Killer Cell Targeting of Pediatric Sarcoma

Osteosarcoma, Ewing sarcoma (EWS), and rhabdomyosarcoma (RMS) are the most common pediatric sarcomas. Conventional therapy for these sarcomas comprises neoadjuvant and adjuvant chemotherapy, surgical resection of the primary tumor and/or radiation therapy. Patients with metastatic, relapsed, or refr...

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Autores principales:	Natacha Omer, Wayne Nicholls, Bronte Ruegg, Fernando Souza-Fonseca-Guimaraes, Gustavo Rodrigues Rossi
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	osteosarcoma Ewing sarcoma rhabdomyosarcoma natural killer immunotherapy Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/e16fca95aa604a308697f240d90ba4f6
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spelling	oai:doaj.org-article:e16fca95aa604a308697f240d90ba4f62021-11-04T07:10:50ZEnhancing Natural Killer Cell Targeting of Pediatric Sarcoma1664-322410.3389/fimmu.2021.791206https://doaj.org/article/e16fca95aa604a308697f240d90ba4f62021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.791206/fullhttps://doaj.org/toc/1664-3224Osteosarcoma, Ewing sarcoma (EWS), and rhabdomyosarcoma (RMS) are the most common pediatric sarcomas. Conventional therapy for these sarcomas comprises neoadjuvant and adjuvant chemotherapy, surgical resection of the primary tumor and/or radiation therapy. Patients with metastatic, relapsed, or refractory tumors have a dismal prognosis due to resistance to these conventional therapies. Therefore, innovative therapeutic interventions, such as immunotherapy, are urgently needed. Recently, cancer research has focused attention on natural killer (NK) cells due their innate ability to recognize and kill tumor cells. Osteosarcoma, EWS and RMS, are known to be sensitive to NK cell cytotoxicity in vitro. In the clinical setting however, NK cell cytotoxicity against sarcoma cells has been mainly studied in the context of allogeneic stem cell transplantation, where a rapid immune reconstitution of NK cells plays a key role in the control of the disease, known as graft-versus-tumor effect. In this review, we discuss the evidence for the current and future strategies to enhance the NK cell-versus-pediatric sarcoma effect, with a clinical focus. The different approaches encompass enhancing antibody-dependent NK cell cytotoxicity, counteracting the NK cell mechanisms of self-tolerance, and developing adoptive NK cell therapy including chimeric antigen receptor-expressing NK cells.Natacha OmerNatacha OmerNatacha OmerWayne NichollsWayne NichollsBronte RueggFernando Souza-Fonseca-GuimaraesGustavo Rodrigues RossiFrontiers Media S.A.articleosteosarcomaEwing sarcomarhabdomyosarcomanatural killerimmunotherapyImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	osteosarcoma Ewing sarcoma rhabdomyosarcoma natural killer immunotherapy Immunologic diseases. Allergy RC581-607
spellingShingle	osteosarcoma Ewing sarcoma rhabdomyosarcoma natural killer immunotherapy Immunologic diseases. Allergy RC581-607 Natacha Omer Natacha Omer Natacha Omer Wayne Nicholls Wayne Nicholls Bronte Ruegg Fernando Souza-Fonseca-Guimaraes Gustavo Rodrigues Rossi Enhancing Natural Killer Cell Targeting of Pediatric Sarcoma
description	Osteosarcoma, Ewing sarcoma (EWS), and rhabdomyosarcoma (RMS) are the most common pediatric sarcomas. Conventional therapy for these sarcomas comprises neoadjuvant and adjuvant chemotherapy, surgical resection of the primary tumor and/or radiation therapy. Patients with metastatic, relapsed, or refractory tumors have a dismal prognosis due to resistance to these conventional therapies. Therefore, innovative therapeutic interventions, such as immunotherapy, are urgently needed. Recently, cancer research has focused attention on natural killer (NK) cells due their innate ability to recognize and kill tumor cells. Osteosarcoma, EWS and RMS, are known to be sensitive to NK cell cytotoxicity in vitro. In the clinical setting however, NK cell cytotoxicity against sarcoma cells has been mainly studied in the context of allogeneic stem cell transplantation, where a rapid immune reconstitution of NK cells plays a key role in the control of the disease, known as graft-versus-tumor effect. In this review, we discuss the evidence for the current and future strategies to enhance the NK cell-versus-pediatric sarcoma effect, with a clinical focus. The different approaches encompass enhancing antibody-dependent NK cell cytotoxicity, counteracting the NK cell mechanisms of self-tolerance, and developing adoptive NK cell therapy including chimeric antigen receptor-expressing NK cells.
format	article
author	Natacha Omer Natacha Omer Natacha Omer Wayne Nicholls Wayne Nicholls Bronte Ruegg Fernando Souza-Fonseca-Guimaraes Gustavo Rodrigues Rossi
author_facet	Natacha Omer Natacha Omer Natacha Omer Wayne Nicholls Wayne Nicholls Bronte Ruegg Fernando Souza-Fonseca-Guimaraes Gustavo Rodrigues Rossi
author_sort	Natacha Omer
title	Enhancing Natural Killer Cell Targeting of Pediatric Sarcoma
title_short	Enhancing Natural Killer Cell Targeting of Pediatric Sarcoma
title_full	Enhancing Natural Killer Cell Targeting of Pediatric Sarcoma
title_fullStr	Enhancing Natural Killer Cell Targeting of Pediatric Sarcoma
title_full_unstemmed	Enhancing Natural Killer Cell Targeting of Pediatric Sarcoma
title_sort	enhancing natural killer cell targeting of pediatric sarcoma
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/e16fca95aa604a308697f240d90ba4f6
work_keys_str_mv	AT natachaomer enhancingnaturalkillercelltargetingofpediatricsarcoma AT natachaomer enhancingnaturalkillercelltargetingofpediatricsarcoma AT natachaomer enhancingnaturalkillercelltargetingofpediatricsarcoma AT waynenicholls enhancingnaturalkillercelltargetingofpediatricsarcoma AT waynenicholls enhancingnaturalkillercelltargetingofpediatricsarcoma AT bronteruegg enhancingnaturalkillercelltargetingofpediatricsarcoma AT fernandosouzafonsecaguimaraes enhancingnaturalkillercelltargetingofpediatricsarcoma AT gustavorodriguesrossi enhancingnaturalkillercelltargetingofpediatricsarcoma
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Enhancing Natural Killer Cell Targeting of Pediatric Sarcoma

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