Two bullets in the gun: combining immunotherapy with chemotherapy to defeat neuroblastoma by targeting adrenergic-mesenchymal plasticity

Frontiers in Immunology

Immunology

Paula Gragera¹  Doriana Fruci¹  Patrizia Tempora¹  Kamila Król¹  Silvia D’Amico¹  Maria Antonietta De Ioris¹  Ombretta Melaiu²  Franco Locatelli³ 

[1] Department of Paediatric Haematology/Oncology and Cell and Gene Therapy, Bambino Gesù Children Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy;Department of Paediatric Haematology/Oncology and Cell and Gene Therapy, Bambino Gesù Children Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy;Department of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Rome, Italy;Department of Paediatric Haematology/Oncology and Cell and Gene Therapy, Bambino Gesù Children Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy;Department of Pediatrics, Catholic University of the Sacred Heart, Rome, Italy;

关键词: neuroblastoma;    tumor microenvironment;    adrenergic to mesenchymal transition;    tumor plasticity;    drug resistance;    metronomic chemotherapy;    immunotherapy;   

DOI  :  10.3389/fimmu.2023.1268645

 received in 2023-07-28, accepted in 2023-09-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 D’Amico, Tempora, Gragera, Król, Melaiu, De Ioris, Locatelli and Fruci