Hlavaty et al. demonstrate that, when cancer cells with high expression of ACSS1 are exposed to acetate, it causes significant metabolic rewiring that promotes cancer cell survival and tumor growth. These studies highlight the potential for targeting ACSS1 in select cancer types.

DiCiaccio et al. conducted a CRISPR viability screen to characterize mechanisms of response and resistance to KDM5 inhibition in basal breast cancer and identified the ZBTB7A transcription factor as a key mediator of KDM5A chromatin binding. Deletion of ZBTB7A alters NF-κB and mitochondrial signaling following KDM5 inhibition.

Root et al. report that expression of individual granulins, 6 kDa subunits of progranulin (88 kDa), is sufficient to prevent disease-associated phenotypes in aged Grn−/− mice. Granulins ameliorated lysosomal dysfunction, microglial activation, lipid dysregulation, and lipofuscin accumulation in Grn−/− mouse brains, suggesting that granulins are the functional components of progranulin.

Immune protection of human pluripotent stem cell (hPSC)-derived grafts remains a key hurdle in regenerative medicine. Barra and Robino et al. engineered hPSCs to express an inert bait protein and bait-specific immunosuppressive chimeric antigen receptor regulatory T cells (CAR-Tregs), accomplishing localized hPSC-derived beta cell immune protection in humanized mice.

Ilaria Elia, guest editor of the cancer metabolism special issue, spoke with Cell Reports about her scientific interests and her lab’s focus on investigating the metabolic interactions between cancer cells and immune cells within the tumor microenvironment. Ilaria also discussed recent developments and future directions in the field.

Wilson et al. demonstrate that KRT14+ leader cells drive ovarian cancer metastasis by promoting immunosuppression. Loss of KRT14+ leader cells impairs tumor progression, while their overexpression accelerates metastasis through chemokine-mediated immune evasion. These findings reveal KRT14+ leader cells as a potential therapeutic target to hinder metastasis and enhance anti-tumor immunity.

Sousa et al. characterized, with time and single-cell resolution, the immune environment of the regenerating skeletal muscle, revealing a profound remodeling of myeloid and lymphoid compartments in aging. This knowledge anticipates the potential of immune cells as targets to improve regenerative capacity in aging.