TY  - INPR
UR  - http://dx.doi.org/10.1016/j.ccell.2023.12.008
ID  - discovery10185107
N2  - Pediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options with less side effects. Since novel and improved immunotherapies may fill this need, we dissect the immunoregulatory interactions in neuroblastoma by single-cell RNA-sequencing of 24 tumors (10 pre- and 14 post-chemotherapy, including 5 pairs) to identify strategies for optimizing immunotherapy efficacy. Neuroblastomas are infiltrated by natural killer (NK), T and B cells, and immunosuppressive myeloid populations. NK cells show reduced cytotoxicity and T cells have a dysfunctional profile. Interaction analysis reveals a vast immunoregulatory network and identifies NECTIN2-TIGIT as a crucial immune checkpoint. Combined blockade of TIGIT and PD-L1 significantly reduces neuroblastoma growth, with complete responses (CR) in vivo. Moreover, addition of TIGIT+PD-L1 blockade to standard relapse treatment in a chemotherapy-resistant Th-ALKF1174L/MYCN 129/SvJ syngeneic model induces CR. In conclusion, our integrative analysis provides promising targets and a rationale for immunotherapeutic combination strategies.
AV  - public
TI  - Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy
Y1  - 2024/01/04/
SN  - 1535-6108
KW  - Neuroblastoma
KW  -  tumor microenvironment
KW  -  immune evasion
KW  -  immunotherapy
KW  -  Immune checkpoint inhibition
KW  -  TIGIT
KW  -  NECTIN2
KW  -  PD-1
KW  -  PD-L1
KW  -  Pediatric oncology
PB  - Elsevier BV
JF  - Cancer Cell
A1  - Wienke, Judith
A1  - Visser, Lindy L
A1  - Kholosy, Waleed M
A1  - Keller, Kaylee M
A1  - Barisa, Marta
A1  - Poon, Evon
A1  - Munnings-Tomes, Sophie
A1  - Himsworth, Courtney
A1  - Calton, Elizabeth
A1  - Rodriguez, Ana
A1  - Bernardi, Ronald
A1  - van den Ham, Femke
A1  - van Hooff, Sander R
A1  - Matser, Yvette AH
A1  - Tas, Michelle L
A1  - Langenberg, Karin PS
A1  - Lijnzaad, Philip
A1  - Borst, Anne L
A1  - Zappa, Elisa
A1  - Bergsma, Francisca J
A1  - Strijker, Josephine GM
A1  - Verhoeven, Bronte M
A1  - Mei, Shenglin
A1  - Kramdi, Amira
A1  - Restuadi, Restuadi
A1  - Sanchez-Bernabeu, Alvaro
A1  - Cornel, Annelisa M
A1  - Holstege, Frank CP
A1  - Gray, Juliet C
A1  - Tytgat, Godelieve AM
A1  - Scheijde-Vermeulen, Marijn A
A1  - Wijnen, Marc HWA
A1  - Dierselhuis, Miranda P
A1  - Straathof, Karin
A1  - Behjati, Sam
A1  - Wu, Wei
A1  - Heck, Albert JR
A1  - Koster, Jan
A1  - Nierkens, Stefan
A1  - Janoueix-Lerosey, Isabelle
A1  - de Krijger, Ronald R
A1  - Baryawno, Ninib
A1  - Chesler, Louis
A1  - Anderson, John
A1  - Caron, Hubert N
A1  - Margaritis, Thanasis
A1  - van Noesel, Max M
A1  - Molenaar, Jan J
N1  - © The Author(s), 2024. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/
ER  -