bims-mecami 2025-01-19 papers

Issue of 2025–01–19
six papers selected by
Oltea Sampetrean, Keio University

Cell Rep. 2025 Jan 10. pii: S2211-1247(24)01557-2. [Epub ahead of print]44(1): 115206

Tumor-induced metabolic immunosuppression: Mechanisms and therapeutic targets.

Metabolic reprogramming in both immune and cancer cells plays a crucial role in the antitumor immune response. Recent studies indicate that cancer metabolism not only sustains carcinogenesis and survival via altered signaling but also modulates immune cell function. Metabolic crosstalk within the tumor microenvironment results in nutrient competition and acidosis, thereby hindering immune cell functionality. Interestingly, immune cells also undergo metabolic reprogramming that enables their proliferation, differentiation, and effector functions. This review highlights the regulation of antitumor immune responses through metabolic reprogramming in cancer and immune cells and explores therapeutic strategies that target these metabolic pathways in cancer immunotherapy, including using chimeric antigen receptor (CAR)-T cells. We discuss innovative combinations of immunotherapy, cellular therapies, and metabolic interventions that could optimize the efficacy of existing treatment protocols.

Keywords: CP: Cancer; CP: Metabolism; antitumor activity of immune cells; cancer; metabolism; therapeutic strategies; tumor microenvironment

DOI: https://doi.org/10.1016/j.celrep.2024.115206

Cancers (Basel). 2025 Jan 06. pii: 155. [Epub ahead of print]17(1):

Metabolic Signaling in the Tumor Microenvironment.

Ryan Clay, Kunyang Li, Lingtao Jin.

Cancer cells must reprogram their metabolism to sustain rapid growth. This is accomplished in part by switching to aerobic glycolysis, uncoupling glucose from mitochondrial metabolism, and performing anaplerosis via alternative carbon sources to replenish intermediates of the tricarboxylic acid (TCA) cycle and sustain oxidative phosphorylation (OXPHOS). While this metabolic program produces adequate biosynthetic intermediates, reducing agents, ATP, and epigenetic remodeling cofactors necessary to sustain growth, it also produces large amounts of byproducts that can generate a hostile tumor microenvironment (TME) characterized by low pH, redox stress, and poor oxygenation. In recent years, the focus of cancer metabolic research has shifted from the regulation and utilization of cancer cell-intrinsic pathways to studying how the metabolic landscape of the tumor affects the anti-tumor immune response. Recent discoveries point to the role that secreted metabolites within the TME play in crosstalk between tumor cell types to promote tumorigenesis and hinder the anti-tumor immune response. In this review, we will explore how crosstalk between metabolites of cancer cells, immune cells, and stromal cells drives tumorigenesis and what effects the competition for resources and metabolic crosstalk has on immune cell function.

Keywords: cancer metabolism; immune response; oncometabolite; tumor microenvironment

DOI: https://doi.org/10.3390/cancers17010155

Adv Exp Med Biol. 2025 ;1464 347-370

Metabolic Reprogramming and Adaption in Breast Cancer Progression and Metastasis.

Qianying Zuo, Yibin Kang.

Recent evidence has revealed that cancer is not solely driven by genetic abnormalities but also by significant metabolic dysregulation. Cancer cells exhibit altered metabolic demands and rewiring of cellular metabolism to sustain their malignant characteristics. Metabolic reprogramming has emerged as a hallmark of cancer, playing a complex role in breast cancer initiation, progression, and metastasis. The different molecular subtypes of breast cancer exhibit distinct metabolic genotypes and phenotypes, offering opportunities for subtype-specific therapeutic approaches. Cancer-associated metabolic phenotypes encompass dysregulated nutrient uptake, opportunistic nutrient acquisition strategies, altered utilization of glycolysis and TCA cycle intermediates, increased nitrogen demand, metabolite-driven gene regulation, and metabolic interactions with the microenvironment. The tumor microenvironment, consisting of stromal cells, immune cells, blood vessels, and extracellular matrix components, influences metabolic adaptations through modulating nutrient availability, oxygen levels, and signaling pathways. Metastasis, the process of cancer spread, involves intricate steps that present unique metabolic challenges at each stage. Successful metastasis requires cancer cells to navigate varying nutrient and oxygen availability, endure oxidative stress, and adapt their metabolic processes accordingly. The metabolic reprogramming observed in breast cancer is regulated by oncogenes, tumor suppressor genes, and signaling pathways that integrate cellular signaling with metabolic processes. Understanding the metabolic adaptations associated with metastasis holds promise for identifying therapeutic targets to disrupt the metastatic process and improve patient outcomes. This chapter explores the metabolic alterations linked to breast cancer metastasis and highlights the potential for targeted interventions in this context.

Keywords: Breast cancer; Circulating tumor cells (CTCs); Epithelial-mesenchymal transition (EMT); Metabolism; Metastasis; Metastatic colonization

DOI: https://doi.org/10.1007/978-3-031-70875-6_17

Int J Mol Med. 2025 Mar;pii: 46. [Epub ahead of print]55(3):

Linking microRNA to metabolic reprogramming and gut microbiota in the pathogenesis of colorectal cancer (Review).

Wan Muhammad Farhan Syafiq Bin Wan Mohd Nor, Soke Chee Kwong, Afiqah Alyaa Md Fuzi, Nur Akmarina Binti Mohd Said, Amira Hajirah Abd Jamil, Yeong Yeh Lee, Soo Ching Lee, Yvonne Ai-Lian Lim, Ivy Chung.

Colorectal cancer (CRC), an emerging public health concern, is one of the leading causes of cancer morbidity and mortality worldwide. An increasing body of evidence shows that dysfunction in metabolic reprogramming is a crucial characteristic of CRC progression. Specifically, metabolic reprogramming abnormalities in glucose, glutamine and lipid metabolism provide the tumour with energy and nutrients to support its rapid cell proliferation and survival. More recently, microRNAs (miRNAs) appear to be involved in the pathogenesis of CRC, including regulatory roles in energy metabolism. In addition, it has been revealed that dysbiosis in CRC might play a key role in impairing the host metabolic reprogramming processes, and while the exact interactions remain unclear, the link may lie with miRNAs. Hence, the aims of the current review include first, to delineate the metabolic reprogramming abnormalities in CRC; second, to explain how miRNAs mediate the aberrant regulations of CRC metabolic pathways; third, linking miRNAs with metabolic abnormalities and dysbiosis in CRC and finally, to discuss the roles of miRNAs as potential biomarkers.

Keywords: colorectal cancer; glucose metabolism; glutamine metabolism; gut microbiota; lipid metabolism; metabolic reprogramming; microRNA; microbiome

DOI: https://doi.org/10.3892/ijmm.2025.5487

Chin J Cancer Res. 2024 Dec 30. 36(6): 652-668

Fatty acid metabolism: A new target for nasopharyngeal carcinoma therapy.

Juan Li, Pengbin Ping, Yanhua Li, Xiaoying Xu.

Lipid metabolic reprogramming is considered one of the most prominent metabolic abnormalities in cancer, and fatty acid metabolism is a key aspect of lipid metabolism. Recent studies have shown that fatty acid metabolism and its related lipid metabolic pathways play important roles in the malignant progression of nasopharyngeal carcinoma (NPC). NPC cells adapt to harsh environments by enhancing biological processes such as fatty acid metabolism, uptake, production, and oxidation, thereby accelerating their growth. In addition, the reprogramming of fatty acid metabolism plays a central role in the tumor microenvironment (TME) of NPC, and the phenotypic transformation of immune cells is closely related to fatty acid metabolism. Moreover, the reprogramming of fatty acid metabolism in NPC contributes to immune escape, which significantly affects disease treatment, progression, recurrence, and metastasis. This review explores recent advances in fatty acid metabolism in NPC and focuses on the interconnections among metabolic reprogramming, tumor immunity, and corresponding therapies. In conclusion, fatty acid metabolism represents a potential target for NPC treatment, and further exploration is needed to develop strategies that target the interaction between fatty acid metabolic reprogramming and immunotherapy.

Keywords: Nasopharyngeal carcinoma; fatty acid metabolism; immunity; lipid metabolism; treatment

DOI: https://doi.org/10.21147/j.issn.1000-9604.2024.06.05

J Hematol Oncol. 2025 Jan 13. 18(1): 6

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges. A critical process induced by TME signaling is the epithelial-mesenchymal transition (EMT), wherein epithelial cells acquire mesenchymal traits, which enhance their motility and invasiveness and promote metastasis and cancer progression. By targeting various components of the TME, novel investigational strategies aim to disrupt the TME's contribution to the EMT, thereby improving treatment efficacy, addressing therapeutic resistance, and offering a nuanced approach to cancer therapy. This review scrutinizes the key players in the TME and the TME's contribution to the EMT, emphasizing avenues to therapeutically disrupt the interactions between the various TME components. Moreover, the article discusses the TME's implications for resistance mechanisms and highlights the current therapeutic strategies toward TME modulation along with potential caveats.

Keywords: Cancer; Cancer-associated fibroblasts (CAFs); Chimeric antigen-receptor (CAR) T-cell therapy; Dendritic cells (DCs); Epithelial-mesenchymal transition (EMT); Extracellular matrix (ECM); Metastasis; Myeloid-derived suppressor cells (MDSCs); Natural killer (NK) cells; T-cell receptor (TCR) therapy; T-cells, B-cells, tumor-associated macrophages (TAMs); Theranostics; Tumor microenvironment (TME); Tumor-associated neutrophils (TANs)

DOI: https://doi.org/10.1186/s13045-024-01634-6