TY - JOUR
T1 - The immune cell atlas of human neuroblastoma
AU - Verhoeven, Bronte Manouk
AU - Mei, Shenglin
AU - Olsen, Thale Kristin
AU - Gustafsson, Karin
AU - Valind, Anders
AU - Lindström, Axel
AU - Gisselsson, David
AU - Fard, Shahrzad Shirazi
AU - Hagerling, Catharina
AU - Kharchenko, Peter V.
AU - Kogner, Per
AU - Johnsen, John Inge
AU - Baryawno, Ninib
PY - 2022/6/21
Y1 - 2022/6/21
N2 - Understanding the complete immune cell composition of human neuroblastoma (NB) is crucial for the development of immunotherapeutics. Here, we perform single-cell RNA sequencing (scRNA-seq) on 19 human NB samples coupled with multiplex immunohistochemistry, survival analysis, and comparison with normal fetal adrenal gland data. We provide a comprehensive immune cell landscape and characterize cell-state changes from normal tissue to NB. Our analysis reveals 27 immune cell subtypes, including distinct subpopulations of myeloid, NK, B, and T cells. Several different cell types demonstrate a survival benefit. In contrast to adult cancers and previous NB studies, we show an increase in inflammatory monocyte cell state when contrasting normal and tumor tissue, while no differences in cytotoxicity and exhaustion score for T cells, nor in Treg activity, are observed. Our receptor-ligand interaction analysis reveals a highly complex interactive network of the NB microenvironment from which we highlight several interactions that we suggest for future therapeutic studies.
AB - Understanding the complete immune cell composition of human neuroblastoma (NB) is crucial for the development of immunotherapeutics. Here, we perform single-cell RNA sequencing (scRNA-seq) on 19 human NB samples coupled with multiplex immunohistochemistry, survival analysis, and comparison with normal fetal adrenal gland data. We provide a comprehensive immune cell landscape and characterize cell-state changes from normal tissue to NB. Our analysis reveals 27 immune cell subtypes, including distinct subpopulations of myeloid, NK, B, and T cells. Several different cell types demonstrate a survival benefit. In contrast to adult cancers and previous NB studies, we show an increase in inflammatory monocyte cell state when contrasting normal and tumor tissue, while no differences in cytotoxicity and exhaustion score for T cells, nor in Treg activity, are observed. Our receptor-ligand interaction analysis reveals a highly complex interactive network of the NB microenvironment from which we highlight several interactions that we suggest for future therapeutic studies.
KW - cancer
KW - human
KW - immune cell landscape
KW - immuno-oncology
KW - immunotherapy
KW - neuroblastoma
KW - pediatric cancer
KW - prognosis
KW - single-cell RNA sequencing
KW - survival
U2 - 10.1016/j.xcrm.2022.100657
DO - 10.1016/j.xcrm.2022.100657
M3 - Article
C2 - 35688160
AN - SCOPUS:85133101304
SN - 2666-3791
VL - 3
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 6
M1 - 100657
ER -