Two bullets in the gun: combining immunotherapy with chemotherapy to defeat neuroblastoma by targeting adrenergic-mesenchymal plasticity
Neuroblastoma (NB) is a childhood tumor that originates in the peripheral sympathetic nervous system and is responsible for 15% of cancer-related deaths in the pediatric population. Despite intensive multimodal treatment, many patients with high-risk NB relapse and develop a therapy-resistant tumor....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1268645/full |
| _version_ | 1797668206384513024 |
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| author | Silvia D’Amico Patrizia Tempora Paula Gragera Kamila Król Ombretta Melaiu Ombretta Melaiu Maria Antonietta De Ioris Franco Locatelli Franco Locatelli Doriana Fruci |
| author_facet | Silvia D’Amico Patrizia Tempora Paula Gragera Kamila Król Ombretta Melaiu Ombretta Melaiu Maria Antonietta De Ioris Franco Locatelli Franco Locatelli Doriana Fruci |
| author_sort | Silvia D’Amico |
| collection | DOAJ |
| description | Neuroblastoma (NB) is a childhood tumor that originates in the peripheral sympathetic nervous system and is responsible for 15% of cancer-related deaths in the pediatric population. Despite intensive multimodal treatment, many patients with high-risk NB relapse and develop a therapy-resistant tumor. One of the phenomena related to therapeutic resistance is intratumor heterogeneity resulting from the adaptation of tumor cells in response to different selective environmental pressures. The transcriptional and epigenetic profiling of NB tissue has recently revealed the existence of two distinct cellular identities in the NB, termed adrenergic (ADRN) and mesenchymal (MES), which can spontaneously interconvert through epigenetic regulation. This phenomenon, known as tumor plasticity, has a major impact on cancer pathogenesis. The aim of this review is to describe the peculiarities of these two cell states, and how their plasticity affects the response to current therapeutic treatments, with special focus on the immunogenic potential of MES cells. Furthermore, we will discuss the opportunity to combine immunotherapy with chemotherapy to counteract NB phenotypic interconversion. |
| first_indexed | 2024-03-11T20:25:32Z |
| format | Article |
| id | doaj.art-9831986078f947f3b3faca75ab236375 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T20:25:32Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9831986078f947f3b3faca75ab2363752023-10-02T15:06:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12686451268645Two bullets in the gun: combining immunotherapy with chemotherapy to defeat neuroblastoma by targeting adrenergic-mesenchymal plasticitySilvia D’Amico0Patrizia Tempora1Paula Gragera2Kamila Król3Ombretta Melaiu4Ombretta Melaiu5Maria Antonietta De Ioris6Franco Locatelli7Franco Locatelli8Doriana Fruci9Department of Paediatric Haematology/Oncology and Cell and Gene Therapy, Bambino Gesù Children Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyDepartment of Paediatric Haematology/Oncology and Cell and Gene Therapy, Bambino Gesù Children Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyDepartment of Paediatric Haematology/Oncology and Cell and Gene Therapy, Bambino Gesù Children Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyDepartment of Paediatric Haematology/Oncology and Cell and Gene Therapy, Bambino Gesù Children Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyDepartment of Paediatric Haematology/Oncology and Cell and Gene Therapy, Bambino Gesù Children Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyDepartment of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Rome, ItalyDepartment of Paediatric Haematology/Oncology and Cell and Gene Therapy, Bambino Gesù Children Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyDepartment of Paediatric Haematology/Oncology and Cell and Gene Therapy, Bambino Gesù Children Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyDepartment of Pediatrics, Catholic University of the Sacred Heart, Rome, ItalyDepartment of Paediatric Haematology/Oncology and Cell and Gene Therapy, Bambino Gesù Children Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, ItalyNeuroblastoma (NB) is a childhood tumor that originates in the peripheral sympathetic nervous system and is responsible for 15% of cancer-related deaths in the pediatric population. Despite intensive multimodal treatment, many patients with high-risk NB relapse and develop a therapy-resistant tumor. One of the phenomena related to therapeutic resistance is intratumor heterogeneity resulting from the adaptation of tumor cells in response to different selective environmental pressures. The transcriptional and epigenetic profiling of NB tissue has recently revealed the existence of two distinct cellular identities in the NB, termed adrenergic (ADRN) and mesenchymal (MES), which can spontaneously interconvert through epigenetic regulation. This phenomenon, known as tumor plasticity, has a major impact on cancer pathogenesis. The aim of this review is to describe the peculiarities of these two cell states, and how their plasticity affects the response to current therapeutic treatments, with special focus on the immunogenic potential of MES cells. Furthermore, we will discuss the opportunity to combine immunotherapy with chemotherapy to counteract NB phenotypic interconversion.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1268645/fullneuroblastomatumor microenvironmentadrenergic to mesenchymal transitiontumor plasticitydrug resistancemetronomic chemotherapy |
| spellingShingle | Silvia D’Amico Patrizia Tempora Paula Gragera Kamila Król Ombretta Melaiu Ombretta Melaiu Maria Antonietta De Ioris Franco Locatelli Franco Locatelli Doriana Fruci Two bullets in the gun: combining immunotherapy with chemotherapy to defeat neuroblastoma by targeting adrenergic-mesenchymal plasticity Frontiers in Immunology neuroblastoma tumor microenvironment adrenergic to mesenchymal transition tumor plasticity drug resistance metronomic chemotherapy |
| title | Two bullets in the gun: combining immunotherapy with chemotherapy to defeat neuroblastoma by targeting adrenergic-mesenchymal plasticity |
| title_full | Two bullets in the gun: combining immunotherapy with chemotherapy to defeat neuroblastoma by targeting adrenergic-mesenchymal plasticity |
| title_fullStr | Two bullets in the gun: combining immunotherapy with chemotherapy to defeat neuroblastoma by targeting adrenergic-mesenchymal plasticity |
| title_full_unstemmed | Two bullets in the gun: combining immunotherapy with chemotherapy to defeat neuroblastoma by targeting adrenergic-mesenchymal plasticity |
| title_short | Two bullets in the gun: combining immunotherapy with chemotherapy to defeat neuroblastoma by targeting adrenergic-mesenchymal plasticity |
| title_sort | two bullets in the gun combining immunotherapy with chemotherapy to defeat neuroblastoma by targeting adrenergic mesenchymal plasticity |
| topic | neuroblastoma tumor microenvironment adrenergic to mesenchymal transition tumor plasticity drug resistance metronomic chemotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1268645/full |
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