Enhancing Neuroblastoma Immunotherapies by Engaging iNKT and NK Cells
Neuroblastoma (NB) is the most common extracranial solid tumor in children and, in the high-risk group, has a 5-year mortality rate of ~50%. The high mortality rate and significant treatment-related morbidities associated with current standard of care therapies belie the critical need for more toler...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00873/full |
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| author | Kevin O. McNerney Spyridon A. Karageorgos Spyridon A. Karageorgos Michael D. Hogarty Hamid Bassiri |
| author_facet | Kevin O. McNerney Spyridon A. Karageorgos Spyridon A. Karageorgos Michael D. Hogarty Hamid Bassiri |
| author_sort | Kevin O. McNerney |
| collection | DOAJ |
| description | Neuroblastoma (NB) is the most common extracranial solid tumor in children and, in the high-risk group, has a 5-year mortality rate of ~50%. The high mortality rate and significant treatment-related morbidities associated with current standard of care therapies belie the critical need for more tolerable and effective treatments for this disease. While the monoclonal antibody dinutuximab has demonstrated the potential for immunotherapy to improve overall NB outcomes, the 5-year overall survival of high-risk patients has not yet substantially changed. The frequency and type of invariant natural killer T cells (iNKTs) and natural killer cells (NKs) has been associated with improved outcomes in several solid and liquid malignancies, including NB. Indeed, iNKTs and NKs inhibit tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs), kill cancer stem cells (CSCs) and neuroblasts, and robustly secrete cytokines to recruit additional immune effectors. These capabilities, and promising pre-clinical and early clinical data suggest that iNKT- and NK-based therapies may hold promise as both stand-alone and combination treatments for NB. In this review we will summarize the biologic features of iNKTs and NKs that confer advantages for NB immunotherapy, discuss the barriers imposed by the NB tumor microenvironment, and examine the current state of such therapies in pre-clinical models and clinical trials. |
| first_indexed | 2024-12-10T23:23:37Z |
| format | Article |
| id | doaj.art-fe49c2117c8b42e196cb1266e70f44ce |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T23:23:37Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fe49c2117c8b42e196cb1266e70f44ce2022-12-22T01:29:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-05-011110.3389/fimmu.2020.00873540136Enhancing Neuroblastoma Immunotherapies by Engaging iNKT and NK CellsKevin O. McNerney0Spyridon A. Karageorgos1Spyridon A. Karageorgos2Michael D. Hogarty3Hamid Bassiri4Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, United StatesSchool of Medicine, European University Cyprus, Nicosia, CyprusDivision of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA, United StatesDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, United StatesDivision of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA, United StatesNeuroblastoma (NB) is the most common extracranial solid tumor in children and, in the high-risk group, has a 5-year mortality rate of ~50%. The high mortality rate and significant treatment-related morbidities associated with current standard of care therapies belie the critical need for more tolerable and effective treatments for this disease. While the monoclonal antibody dinutuximab has demonstrated the potential for immunotherapy to improve overall NB outcomes, the 5-year overall survival of high-risk patients has not yet substantially changed. The frequency and type of invariant natural killer T cells (iNKTs) and natural killer cells (NKs) has been associated with improved outcomes in several solid and liquid malignancies, including NB. Indeed, iNKTs and NKs inhibit tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs), kill cancer stem cells (CSCs) and neuroblasts, and robustly secrete cytokines to recruit additional immune effectors. These capabilities, and promising pre-clinical and early clinical data suggest that iNKT- and NK-based therapies may hold promise as both stand-alone and combination treatments for NB. In this review we will summarize the biologic features of iNKTs and NKs that confer advantages for NB immunotherapy, discuss the barriers imposed by the NB tumor microenvironment, and examine the current state of such therapies in pre-clinical models and clinical trials.https://www.frontiersin.org/article/10.3389/fimmu.2020.00873/fullinvariant natural killer T cellsnatural killer cellscancer immunotherapyimmunotherapyneuroblastomatumor microenvironment |
| spellingShingle | Kevin O. McNerney Spyridon A. Karageorgos Spyridon A. Karageorgos Michael D. Hogarty Hamid Bassiri Enhancing Neuroblastoma Immunotherapies by Engaging iNKT and NK Cells Frontiers in Immunology invariant natural killer T cells natural killer cells cancer immunotherapy immunotherapy neuroblastoma tumor microenvironment |
| title | Enhancing Neuroblastoma Immunotherapies by Engaging iNKT and NK Cells |
| title_full | Enhancing Neuroblastoma Immunotherapies by Engaging iNKT and NK Cells |
| title_fullStr | Enhancing Neuroblastoma Immunotherapies by Engaging iNKT and NK Cells |
| title_full_unstemmed | Enhancing Neuroblastoma Immunotherapies by Engaging iNKT and NK Cells |
| title_short | Enhancing Neuroblastoma Immunotherapies by Engaging iNKT and NK Cells |
| title_sort | enhancing neuroblastoma immunotherapies by engaging inkt and nk cells |
| topic | invariant natural killer T cells natural killer cells cancer immunotherapy immunotherapy neuroblastoma tumor microenvironment |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00873/full |
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