BibTex format
@article{Reen:2025:10.1126/sciadv.adn2811,
author = {Reen, V and D'Ambrosio, M and Søgaard, PP and Tyson, K and Leeke, BJ and Clément, I and Dye, ICA and Pombo, J and Kuba, A and Lan, Y and Burr, J and Bomann, IC and Kalyva, M and Birch, J and Khadayate, S and Young, G and Provencher, D and Mes-Masson, A-M and Vernia, S and McGranahan, N and Brady, HJM and Rodier, F and Nativio, R and Percharde, M and McNeish, IA and Gil, J},
doi = {10.1126/sciadv.adn2811},
journal = {Science Advances},
title = {SMARCA4 regulates the NK-mediated killing of senescent cells},
url = {http://dx.doi.org/10.1126/sciadv.adn2811},
volume = {11},
year = {2025}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Induction of senescence by chemotherapeutic agents arrests cancer cells and activates immune surveillance responses to contribute to therapy outcomes. In this investigation, we searched for ways to enhance the NK-mediated elimination of senescent cells. We used a staggered screen approach, first identifying siRNAs potentiating the secretion of immunomodulatory cytokines to later test for their ability to enhance NK-mediated killing of senescent cells. We identified that genetic or pharmacological inhibition of SMARCA4 enhanced senescent cell elimination by NK cells. SMARCA4 expression is elevated during senescence and its inhibition derepresses repetitive elements, inducing the SASP via activation of cGAS/STING and MAVS/MDA5 pathways. Moreover, a PROTAC targeting SMARCA4 synergized with cisplatin to increase the infiltration of CD8 T cells and mature, activated NK cells in an immunocompetent model of ovarian cancer. Our results indicate that SMARCA4 inhibitors enhance NK-mediated surveillance of senescent cells and may represent senotherapeutic interventions for ovarian cancer.
AU - Reen,V
AU - D'Ambrosio,M
AU - Søgaard,PP
AU - Tyson,K
AU - Leeke,BJ
AU - Clément,I
AU - Dye,ICA
AU - Pombo,J
AU - Kuba,A
AU - Lan,Y
AU - Burr,J
AU - Bomann,IC
AU - Kalyva,M
AU - Birch,J
AU - Khadayate,S
AU - Young,G
AU - Provencher,D
AU - Mes-Masson,A-M
AU - Vernia,S
AU - McGranahan,N
AU - Brady,HJM
AU - Rodier,F
AU - Nativio,R
AU - Percharde,M
AU - McNeish,IA
AU - Gil,J
DO - 10.1126/sciadv.adn2811
PY - 2025///
SN - 2375-2548
TI - SMARCA4 regulates the NK-mediated killing of senescent cells
T2 - Science Advances
UR - http://dx.doi.org/10.1126/sciadv.adn2811
UR - https://www.science.org/doi/10.1126/sciadv.adn2811
VL - 11
ER -