Retinoic acid receptor activation reprograms senescence response and enhances anti-tumor activity of natural killer cells

Colucci, Manuel, Zumerle, Sara, Bressan, Silvia, Gianfanti, Federico, Troiani, Martina, Valdata, Aurora, D'Ambrosio, Mariantonietta, Pasquini, Emiliano, Varesi, Angelica, Cogo, Francesca, Mosole, Simone, Dongilli, Cristina, Desbats, Maria Andrea, Contu, Liliana, Revankdar, Ajinkya, Chen, Jingjing, Kalathur, Madhuri, Perciato, Maria Luna, Basilotta, Rossella, Endre, Laczko, Schauer, Stefan, Othman, Alaa, Guccini, Ilaria, Saponaro, Miriam, Maraccani, Luisa, Bancaro, Nicolò, Lai, Ping, Liu, Lei, Pernigoni, Nicolò, Mele, Federico, Merler, Sara, Trotman, Lloyd C, Guarda, Greta, Calì, Bianca, Montopoli, Monica, Alimonti, Andrea (February 2024) Retinoic acid receptor activation reprograms senescence response and enhances anti-tumor activity of natural killer cells. Cancer Cell. S1535-6108(24)00048. ISSN 1535-6108 (Public Dataset)

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Abstract

Cellular senescence can exert dual effects in tumors, either suppressing or promoting tumor progression. The senescence-associated secretory phenotype (SASP), released by senescent cells, plays a crucial role in this dichotomy. Consequently, the clinical challenge lies in developing therapies that safely enhance senescence in cancer, favoring tumor-suppressive SASP factors over tumor-promoting ones. Here, we identify the retinoic-acid-receptor (RAR) agonist adapalene as an effective pro-senescence compound in prostate cancer (PCa). Reactivation of RARs triggers a robust senescence response and a tumor-suppressive SASP. In preclinical mouse models of PCa, the combination of adapalene and docetaxel promotes a tumor-suppressive SASP that enhances natural killer (NK) cell-mediated tumor clearance more effectively than either agent alone. This approach increases the efficacy of the allogenic infusion of human NK cells in mice injected with human PCa cells, suggesting an alternative therapeutic strategy to stimulate the anti-tumor immune response in "immunologically cold" tumors.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > senescence
CSHL Authors:	Trotman, Lloyd C.
Communities:	CSHL labs > Trotman lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	27 February 2024
Date Deposited:	18 Mar 2024 12:45
Last Modified:	11 Apr 2024 14:46
PMCID:	PMC11003464
Related URLs:	Publisher
Dataset ID:	https://www.pcaprofiler.com/ GEO: GSE253331
URI:	https://repository.cshl.edu/id/eprint/41465

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