TY  - JOUR
AU  - Miao, Beiping
AU  - Hu, Zhaoqing
AU  - Mezzadra, Riccardo
AU  - Hoeijmakers, Lotte
AU  - Fauster, Astrid
AU  - Du, Shangce
AU  - Yang, Zhi
AU  - Sator-Schmitt, Melanie
AU  - Engel, Helena
AU  - Li, Xueshen
AU  - Broderick, Caroline
AU  - Jin, Guangzhi
AU  - Gomez-Eerland, Raquel
AU  - Rozeman, Lisette
AU  - Lei, Xin
AU  - Matsuo, Hitoshi
AU  - Yang, Chen
AU  - Hofland, Ingrid
AU  - Peters, Dennis
AU  - Broeks, Annegien
AU  - Laport, Elke
AU  - Fitz, Annika
AU  - Zhao, Xiyue
AU  - Mahmoud, Mohamed Abdalla Abdelaziz
AU  - Ma, Xiujian
AU  - Sander, Sandrine
AU  - Liu, Hai-Kun
AU  - Cui, Guoliang
AU  - Gan, Yu
AU  - Wu, Wei
AU  - Xiao, Yanling
AU  - Heck, Albert J R
AU  - Guan, Wenxian
AU  - Lowe, Scott W
AU  - Horlings, Hugo M
AU  - Wang, Cun
AU  - Brummelkamp, Thijn R
AU  - Blank, Christian U
AU  - Schumacher, Ton N M
AU  - Sun, Chong
TI  - CMTM6 shapes antitumor T cell response through modulating protein expression of CD58 and PD-L1.
JO  - Cancer cell
VL  - 41
IS  - 10
SN  - 1535-6108
CY  - New York, NY
PB  - Elsevier
M1  - DKFZ-2023-02285
SP  - 1817 - 1828.e9
PY  - 2023
N1  - DKFZ-ZMBH Alliance / #EA:D250#LA:D250#
AB  - The dysregulated expression of immune checkpoint molecules enables cancer cells to evade immune destruction. While blockade of inhibitory immune checkpoints like PD-L1 forms the basis of current cancer immunotherapies, a deficiency in costimulatory signals can render these therapies futile. CD58, a costimulatory ligand, plays a crucial role in antitumor immune responses, but the mechanisms controlling its expression remain unclear. Using two systematic approaches, we reveal that CMTM6 positively regulates CD58 expression. Notably, CMTM6 interacts with both CD58 and PD-L1, maintaining the expression of these two immune checkpoint ligands with opposing functions. Functionally, the presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and response to PD-L1-PD-1 blockade. Collectively, these findings provide fundamental insights into CD58 regulation, uncover a shared regulator of stimulatory and inhibitory immune checkpoints, and highlight the importance of tumor-intrinsic CMTM6 and CD58 expression in antitumor immune responses.
LB  - PUB:(DE-HGF)16
C6  - pmid:37683639
DO  - DOI:10.1016/j.ccell.2023.08.008
UR  - https://inrepo02.dkfz.de/record/285250
ER  -