Tito Sandoval: Cubillos-Ruiz Lab’s latest study about iron chelation therapy for ovarian cancer
Tito Sandoval, Senior Scientist at Washington University School of Medicine in St. Louis, shared on X about a paper titled “Iron Chelation Therapy Elicits Innate Immune Control of Metastatic Ovarian Cancer” published on Cancer Discovery.
Authors: Tito A. Sandoval, Camilla Salvagno, Chang-Suk Chae, Deepika Awasthi, Paolo Giovanelli, Matias Marin Falco, Sung-Min Hwang, Eli Teran-Cabanillas, Lasse Suominen, Takahiro Yamazaki, Hui-Hsuan Kuo, Jenna E. Moyer, M. Laura Martin, Jyothi Manohar, Kihwan Kim, Maria A. Sierra, Yusibeska Ramos, Chen Tan, Alexander Emmanuelli, Minkyung Song, Diana K. Morales, Dmitriy Zamarin, Melissa K. Frey, Evelyn Cantillo, Eloise Chapman-Davis, Kevin Holcomb, Christopher E. Mason, Lorenzo Galluzzi, Zhen Ni Zhou, Anna Vaharautio, Suzanne M. Cloonan, Juan R. Cubillos-Ruiz.
“New Research Alert! Cubillos-Ruiz Lab’s latest study in Cancer Discovery reveals that iron chelation therapy can significantly impact metastatic ovarian cancer by activating innate immune responses. Read the full study here.
Background: High-grade serous ovarian cancer (HGSOC) is notoriously resistant to treatment and thrives on iron accumulation. This study explores the role of iron chelation using deferiprone, an FDA-approved drug.
Iron Status in HGSOC patients: Iron-related gene signatures are overexpressed in ovarian tumors and correlate with poor prognosis. We found high levels of iron and an abundance of proteins related to iron transport in the malignant ascites of ovarian cancer patients.
Validation: These findings were validated in mouse models of ovarian cancer, showing similar iron accumulation and iron-related gene expression profiles specifically in tumor cells.
Synergy with Chemotherapy: Combining deferiprone with cisplatin significantly prolongs survival in mice. Deferiprone shows efficacy both as a single agent and in combination with cisplatin.
Immune Response: Deferiprone treatment results in significant accumulation of NK cells in the peritoneal cavity and omentum, which is crucial for its therapeutic effects.
Activation of Gene Programs: Deferiprone induces immunostimulatory gene programs in murine ovarian cancer cells and human ovarian cancer organoids.
Mechanism: Deferiprone triggers innate immune signaling in malignant cells by triggering mitochondrial DNA release, thus activating the cGAS-STING-IRF3 pathway. At the same time, it activates DNA damage responses. This results in the production of type I IFN and NK-activating ligands.
Protective NK Cell Responses: Deferiprone-induced type I IFN drives protective NK cell responses by enhancing IL-15 expression in tumor-associated DCs.
Clinical Implications: We propose that disrupting iron accumulation in the tumor microenvironment may represent a new immunotherapeutic approach for aggressive malignancies, like ovarian cancer, that are refractory to current T cell-centric modalities such as immune checkpoint blockade and adoptive cellular therapy.”
Source: Tito Sandoval/X
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