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Comment
. 2022 Sep 22;11(1):2127274.
doi: 10.1080/2162402X.2022.2127274. eCollection 2022.

Type I interferon induces cancer stem cells-mediated chemotherapy resistance

Mara De Martino  1 , Claire Vanpouille-Box  1   2
Affiliations
Comment

Type I interferon induces cancer stem cells-mediated chemotherapy resistance

Mara De Martino et al. Oncoimmunology. .

Abstract

In a recent study in Nature Immunology, Musella et al. demonstrate that suboptimal type I interferon (IFN-I) signaling in tumors undergoing immunogenic cell death (ICD) facilitates the accumulation of cancer stem cells (CSCs) by triggering the epigenetic regulator lysine demethylase 1B (KDM1B). KDM1B stands out as a promising target for the development of novel strategies to improve anti-cancer responses driven by ICD.

Keywords: Chemotherapy; KDM1B; cancer stem cells; epigenetic immune escape; immunogenic cell death; interferon type I.

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Conflict of interest statement

Authors have nothing to disclose pertaining to this work.

Figures

Figure 1.
Figure 1.
Chemotherapy-induced IFN-I promotes KDM1B-mediated CSCs accumulation and tumor resistance. Chemotherapeutics can induce immunogenic cell death (i.e., oxaliplatin or doxorubicin), resulting in the release of damage-associated molecular patterns (DAMPs), such as type I interferons (IFN-I), that stimulate anti-tumor immunity mediated by dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs). Depending on the dose and timing of the IFN-I signaling, IFN-I induces an epigenetic remodeling mediated by the lysine demethylase 1B (KDM1B) that leads to the accumulation of cancer stem cells (CSCs). These CSCs promote tumorigenicity, chemoresistance, immunoevasion and metastasis. Inhibition of KDM1B with tranylcypromine (TCP) in combination with immunogenic chemotherapy, prevented the accumulation of CSCs and lead to tumor control.
See this image and copyright information in PMC

Comment on

  • Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B.
    Musella M, Guarracino A, Manduca N, Galassi C, Ruggiero E, Potenza A, Maccafeo E, Manic G, Mattiello L, Soliman Abdel Rehim S, Signore M, Pietrosanto M, Helmer-Citterich M, Pallocca M, Fanciulli M, Bruno T, De Nicola F, Corleone G, Di Benedetto A, Ercolani C, Pescarmona E, Pizzuti L, Guidi F, Sperati F, Vitale S, Macchia D, Spada M, Schiavoni G, Mattei F, De Ninno A, Businaro L, Lucarini V, Bracci L, Aricò E, Ziccheddu G, Facchiano F, Rossi S, Sanchez M, Boe A, Biffoni M, De Maria R, Vitale I, Sistigu A. Musella M, et al. Nat Immunol. 2022 Sep;23(9):1379-1392. doi: 10.1038/s41590-022-01290-3. Epub 2022 Aug 24. Nat Immunol. 2022. PMID: 36002648 Free PMC article.

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