Mitochondria are organelles that are able to adjust and respond to different stressors and metabolic needs within a cell, showcasing their plasticity and dynamic nature. These abilities allow them to effectively coordinate various cellular functions. Mitochondrial dynamics refers to the changing process of fission, fusion, mitophagy and transport, which is crucial for optimal function in signal transduction and metabolism. An imbalance in mitochondrial dynamics can disrupt mitochondrial function, leading to abnormal cellular fate, and a range of diseases, including neurodegenerative disorders, metabolic diseases, cardiovascular diseases and cancers. Herein, we review the mechanism of mitochondrial dynamics, and its impacts on cellular function. We also delve into the changes that occur in mitochondrial dynamics during health and disease, and offer novel perspectives on how to target the modulation of mitochondrial dynamics.

Background & Aims: Liver cancer stem cells (LCSCs) mediate therapeutic resistance and correlate with poor outcomes in patients with hepatocellular carcinoma (HCC). Fibroblast growth factor (FGF)-19 is a crucial oncogenic driver gene in HCC and correlates with poor prognosis. However, whether FGF19 signaling regulates the self-renewal of LCSCs is unknown.

Metabolic reprogramming drives the development of an immunosuppressive tumor microenvironment (TME) through various pathways, contributing to cancer progression and reducing the effectiveness of anticancer immunotherapy. However, our understanding of the metabolic landscape within the tumor-immune context has been limited by conventional metabolic measurements, which have not provided comprehensive insights into the spatiotemporal heterogeneity of metabolism within TME. The emergence of single-cell, spatial, and in vivo metabolomic technologies has now enabled detailed and unbiased analysis, revealing unprecedented spatiotemporal heterogeneity that is particularly valuable in the field of cancer immunology. This review summarizes the methodologies of metabolomics and metabolic regulomics that can be applied to the study of cancer-immunity across single-cell, spatial, and in vivo dimensions, and systematically assesses their benefits and limitations.

Fibroblast growth factors (FGFs) are a versatile family of peptide growth factors that are involved in various biological functions, including cell growth and differentiation, embryonic development, angiogenesis, and metabolism. Abnormal FGF/FGF receptor (FGFR) signaling has been implicated in the pathogenesis of multiple diseases such as cancer, metabolic diseases, and inflammatory diseases. It is worth noting that macrophage polarization, which involves distinct functional phenotypes, plays a crucial role in tissue repair, homeostasis maintenance, and immune responses. Recent evidence suggests that FGF/FGFR signaling closely participates in the polarization of macrophages, indicating that they could be potential targets for therapeutic manipulation of diseases associated with dysfunctional macrophages. In this article, we provide an overview of the structure, function, and downstream regulatory pathways of FGFs, as well as crosstalk between FGF signaling and macrophage polarization. Additionally, we summarize the potential application of harnessing FGF signaling to modulate macrophage polarization.

Rationale: The introduction of combination therapy utilizing tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors for advanced hepatocellular carcinoma (HCC) has significantly altered the management of affected patients. However, the absence of predictive biomarkers to identify those who would derive the greatest benefit from this combination therapy underscores the necessity for further enhancements in its efficacy.

Myeloid‐derived suppressor cells (MDSCs) represent a significant immunosuppressive population within the tumor microenvironment of colorectal cancer (CRC). Their activity has been strongly associated with the reprogramming of cholesterol metabolism, although the underlying mechanisms remain unclear. To investigate this, we generated myeloid‐specific cholesterol 25‐hydroxylase (CH25H) knockdown mice and differentiated bone marrow cells from wild‐type (WT) or Ch25h ^f/f Lyz2 ^Cre mice into MDSCs, subsequently treating them with 25‐hydroxycholesterol (25HC). Immune function was evaluated using flow cytometry, Western blotting, and real‐time polymerase chain reaction (PCR). Our findings indicated that CH25H and its metabolite 25HC were significantly upregulated in CRC‐associated MDSCs. The loss of CH25H impaired their immunosuppressive capacity by reducing arginase‐1 (ARG1) expression, an effect that was restored by 25HC supplementation. Mechanistically, 25HC suppressed the activation of the cyclic guanosine monophosphate–adenosine monophosphate synthase–stimulator of interferon genes (cGAS–STING) pathway and the downstream tank‐binding kinase 1 (TBK1). TBK1 formed a complex with receptor‐interacting protein kinase 3 (RIPK3), thereby repressing ARG1 expression through phosphorylation‐dependent signaling. Collectively, these findings reveal a previously unrecognized CH25H–25HC–STING axis in MDSC‐mediated immune regulation and suggest that targeting cholesterol metabolism may provide a promising therapeutic strategy for CRC immunotherapy.