bims-mecami Biomed News
on Metabolic interactions between cancer cells and their microenvironment
Issue of 2024–06–23
six papers selected by
Oltea Sampetrean, Keio University
  1. Metabolic Reprogramming in Tumor Immune Microenvironment: Impact on Immune Cell Function and Therapeutic Implications.
  2. Nicotinamide metabolism face-off between macrophages and fibroblasts manipulates the microenvironment in gastric cancer.
  3. Tumor glucose metabolism and the T cell glycocalyx: implication for T cell function.
  4. The Role of Metabolic Reprogramming in the Tumor Immune Microenvironment: Mechanisms and Opportunities for Immunotherapy in Hepatocellular Carcinoma.
  5. Fasting reshapes tissue-specific niches to improve NK cell-mediated anti-tumor immunity.
  6. Apoptosis, a Metabolic "Head-to-Head" between Tumor and T Cells: Implications for Immunotherapy.
  1. Cancer Lett. 2024 Jun 19. pii: S0304-3835(24)00471-3. [Epub ahead of print] 217076
    Metabolic Reprogramming in Tumor Immune Microenvironment: Impact on Immune Cell Function and Therapeutic Implications.
    Yuqiang Liu, Yu Zhao, Huisheng Song, Yunting Li, Zihao Liu, Zhiming Ye, Jianzhu Zhao, Yuzheng Wu, Jun Tang, Maojin Yao.
      Understanding of the metabolic reprogramming has revolutionized our insights into tumor progression and potential treatment. This review concentrates on the aberrant metabolic pathways in cancer cells within the tumor microenvironment (TME). Cancer cells differ from normal cells in their metabolic processing of glucose, amino acids, and lipids in order to adapt to heightened biosynthetic and energy needs. These metabolic shifts, which crucially alter lactic acid, amino acid and lipid metabolism, affect not only tumor cell proliferation but also TME dynamics. This review also explores the reprogramming of various immune cells in the TME. From a therapeutic standpoint, targeting these metabolic alterations represents a novel cancer treatment strategy. This review also discusses approaches targeting the regulation of metabolism of different nutrients in tumor cells and influencing the tumor microenvironment to enhance the immune response. In summary, this review summarizes metabolic reprogramming in cancer and its potential as a target for innovative therapeutic strategies, offering fresh perspectives on cancer treatment.
    Keywords:  Immune cell; Immunotherapy; Tumor metabolic reprogramming; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.canlet.2024.217076
  2. Cell Metab. 2024 Jun 12. pii: S1550-4131(24)00189-X. [Epub ahead of print]
    Nicotinamide metabolism face-off between macrophages and fibroblasts manipulates the microenvironment in gastric cancer.
    Yu Jiang, Yawen Wang, Guofeng Chen, Fei Sun, Qijing Wu, Qiong Huang, Dongqiang Zeng, Wenjun Qiu, Jiao Wang, Zhiqi Yao, Bishan Liang, Shaowei Li, Jianhua Wu, Na Huang, Yuanyuan Wang, Jingsong Chen, Xiaohui Zhai, Li Huang, Beibei Xu, Masami Yamamoto, Tetsuya Tsukamoto, Sachiyo Nomura, Wangjun Liao, Min Shi.
      Immune checkpoint blockade has led to breakthroughs in the treatment of advanced gastric cancer. However, the prominent heterogeneity in gastric cancer, notably the heterogeneity of the tumor microenvironment, highlights the idea that the antitumor response is a reflection of multifactorial interactions. Through transcriptomic analysis and dynamic plasma sample analysis, we identified a metabolic "face-off" mechanism within the tumor microenvironment, as shown by the dual prognostic significance of nicotinamide metabolism. Specifically, macrophages and fibroblasts expressing the rate-limiting enzymes nicotinamide phosphoribosyltransferase and nicotinamide N-methyltransferase, respectively, regulate the nicotinamide/1-methylnicotinamide ratio and CD8+ T cell function. Mechanistically, nicotinamide N-methyltransferase is transcriptionally activated by the NOTCH pathway transcription factor RBP-J and is further inhibited by macrophage-derived extracellular vesicles containing nicotinamide phosphoribosyltransferase via the SIRT1/NICD axis. Manipulating nicotinamide metabolism through autologous injection of extracellular vesicles restored CD8+ T cell cytotoxicity and the anti-PD-1 response in gastric cancer.
    Keywords:  crosstalk; face-off; fibroblast; gastric cancer; immune checkpoint blockade; macrophage; nicotinamide metabolism; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.cmet.2024.05.013
  3. Front Immunol. 2024 ;15 1409238
    Tumor glucose metabolism and the T cell glycocalyx: implication for T cell function.
    Fabian Schuurmans, Kyra E Wagemans, Gosse J Adema, Lenneke A M Cornelissen.
      The T cell is an immune cell subset highly effective in eliminating cancer cells. Cancer immunotherapy empowers T cells and occupies a solid position in cancer treatment. The response rate, however, remains relatively low (<30%). The efficacy of immunotherapy is highly dependent on T cell infiltration into the tumor microenvironment (TME) and the ability of these infiltrated T cells to sustain their function within the TME. A better understanding of the inhibitory impact of the TME on T cells is crucial to improve cancer immunotherapy. Tumor cells are well described for their switch into aerobic glycolysis (Warburg effect), resulting in high glucose consumption and a metabolically distinct TME. Conversely, glycosylation, a predominant posttranslational modification of proteins, also relies on glucose molecules. Proper glycosylation of T cell receptors influences the immunological synapse between T cells and tumor cells, thereby affecting T cell effector functions including their cytolytic and cytostatic activities. This review delves into the complex interplay between tumor glucose metabolism and the glycocalyx of T cells, shedding light on how the TME can induce alterations in the T cell glycocalyx, which can subsequently influence the T cell's ability to target and eliminate tumor cells.
    Keywords:  T cell glycocalyx; glycobiology; metabolism; tumor immunity; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2024.1409238
  4. Int J Mol Sci. 2024 May 21. pii: 5584. [Epub ahead of print]25(11):
    The Role of Metabolic Reprogramming in the Tumor Immune Microenvironment: Mechanisms and Opportunities for Immunotherapy in Hepatocellular Carcinoma.
    Nan Hu, Haiyang Li, Changcheng Tao, Ting Xiao, Weiqi Rong.
      As one of the emerging hallmarks of tumorigenesis and tumor progression, metabolic remodeling is common in the tumor microenvironment. Hepatocellular carcinoma (HCC) is the third leading cause of global tumor-related mortality, causing a series of metabolic alterations in response to nutrient availability and consumption to fulfill the demands of biosynthesis and carcinogenesis. Despite the efficacy of immunotherapy in treating HCC, the response rate remains unsatisfactory. Recently, research has focused on metabolic reprogramming and its effects on the immune state of the tumor microenvironment, and immune response rate. In this review, we delineate the metabolic reprogramming observed in HCC and its influence on the tumor immune microenvironment. We discuss strategies aimed at enhancing response rates and overcoming immune resistance through metabolic interventions, focusing on targeting glucose, lipid, or amino acid metabolism, as well as systemic regulation.
    Keywords:  hepatocellular carcinoma; immunotherapy; metabolic intervention; metabolic reprogramming; tumor microenvironment
    DOI:  https://doi.org/10.3390/ijms25115584
  5. Immunity. 2024 Jun 12. pii: S1074-7613(24)00275-9. [Epub ahead of print]
    Fasting reshapes tissue-specific niches to improve NK cell-mediated anti-tumor immunity.
    Rebecca B Delconte, Mark Owyong, Endi K Santosa, Katja Srpan, Sam Sheppard, Tomi J McGuire, Aamna Abbasi, Carlos Diaz-Salazar, Jerold Chun, Inez Rogatsky, Katharine C Hsu, Stefan Jordan, Miriam Merad, Joseph C Sun.
      Fasting is associated with improved outcomes in cancer. Here, we investigated the impact of fasting on natural killer (NK) cell anti-tumor immunity. Cyclic fasting improved immunity against solid and metastatic tumors in an NK cell-dependent manner. During fasting, NK cells underwent redistribution from peripheral tissues to the bone marrow (BM). In humans, fasting also reduced circulating NK cell numbers. NK cells in the spleen of fasted mice were metabolically rewired by elevated concentrations of fatty acids and glucocorticoids, augmenting fatty acid metabolism via increased expression of the enzyme CPT1A, and Cpt1a deletion impaired NK cell survival and function in this setting. In parallel, redistribution of NK cells to the BM during fasting required the trafficking mediators S1PR5 and CXCR4. These cells were primed by an increased pool of interleukin (IL)-12-expressing BM myeloid cells, which improved IFN-γ production. Our findings identify a link between dietary restriction and optimized innate immune responses, with the potential to enhance immunotherapy strategies.
    Keywords:  NK cells; anti-tumor responses; fasting; immunometabolism; innate immunity; metabolism
    DOI:  https://doi.org/10.1016/j.immuni.2024.05.021
  6. Cells. 2024 May 27. pii: 924. [Epub ahead of print]13(11):
    Apoptosis, a Metabolic "Head-to-Head" between Tumor and T Cells: Implications for Immunotherapy.
    Ornella Franzese, Pietro Ancona, Nicoletta Bianchi, Gianluca Aguiari.
      Induction of apoptosis represents a promising therapeutic approach to drive tumor cells to death. However, this poses challenges due to the intricate nature of cancer biology and the mechanisms employed by cancer cells to survive and escape immune surveillance. Furthermore, molecules released from apoptotic cells and phagocytes in the tumor microenvironment (TME) can facilitate cancer progression and immune evasion. Apoptosis is also a pivotal mechanism in modulating the strength and duration of anti-tumor T-cell responses. Combined strategies including molecular targeting of apoptosis, promoting immunogenic cell death, modulating immunosuppressive cells, and affecting energy pathways can potentially overcome resistance and enhance therapeutic outcomes. Thus, an effective approach for targeting apoptosis within the TME should delicately balance the selective induction of apoptosis in tumor cells, while safeguarding survival, metabolic changes, and functionality of T cells targeting crucial molecular pathways involved in T-cell apoptosis regulation. Enhancing the persistence and effectiveness of T cells may bolster a more resilient and enduring anti-tumor immune response, ultimately advancing therapeutic outcomes in cancer treatment. This review delves into the pivotal topics of this multifaceted issue and suggests drugs and druggable targets for possible combined therapies.
    Keywords:  T cells; apoptosis; cancer
    DOI:  https://doi.org/10.3390/cells13110924
This page is being maintained by Thomas Krichel. It was last updated on 2025‒01‒26 at 1:51.