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. 2023 Aug 21;14(8):538.
doi: 10.1038/s41419-023-06079-2.

Cancer stem cell immunoediting by IFNγ

Claudia Galassi  1 , Lorenzo Galluzzi  2   3   4
Affiliations

Cancer stem cell immunoediting by IFNγ

Claudia Galassi et al. Cell Death Dis. .

Abstract

The secretion of interferon gamma (IFNG, best known as IFNγ) by immune effector cells generally mediates potent anticancer effects. Recent data from Beziaud et al. demonstrate that—at least in some circumstances—IFNγ can edit the breast cancer microenvironment to promote stemness, disease progression and resistance to (immuno)therapy.

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Conflict of interest statement

CG has no conflicts of interest to declare. LG is/has been holding research contracts with Lytix Biopharma, Promontory and Onxeo, has received consulting/advisory honoraria from Boehringer Ingelheim, AstraZeneca, OmniSEQ, Onxeo, The Longevity Labs, Inzen, Imvax, Sotio, Promontory, Noxopharm, EduCom, and the Luke Heller TECPR2 Foundation, and holds Promontory stock options.

Figures

Fig. 1
Fig. 1. Detrimental effects of immunoediting on cancer stemness, tumor progression and resistance to therapy.
Potent type I interferon (IFN) responses as driven by some (immuno)therapeutics appear to elicit robust CD8+ cytotoxic T lymphocyte (CTL) activity coupled with the abundant secretion of interferon gamma (IFNG, best known as IFNγ) and ultimately conducive to immunological tumor eradication (A). On the contrary, suboptimal type I IFN and/or IFNG signaling drive immunoediting in the tumor microenvironment (TME) in support of the selection of pre-existing—and/or generation of novel—cancer stem cells (CSCs), ultimately favoring accelerated disease progression in the context of (immuno)therapy resistance. At least in some settings, branched chain amino acid transaminase 1 (BCAT1) inhibition may limit CSC accumulation as driven by suboptimal type I IFN and/or IFNG signaling, thus restoring successful anticancer immunosurveillance (B). DC dendritic cell.
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