bims-mecami Biomed News
on Metabolic interactions between cancer cells and their microenvironment
Issue of 2024–06–30
seven papers selected by
Oltea Sampetrean, Keio University
  1. Metabolic reprogramming of the tumor microenvironment to enhance immunotherapy.
  2. Nanoscale Metal-Organic Layer Reprograms Cellular Metabolism to Enhance Photodynamic Therapy and Antitumor Immunity.
  3. Metabolic dialogues: regulators of chimeric antigen receptor T cell function in the tumor microenvironment.
  4. Glycolysis in the tumor microenvironment: a driver of cancer progression and a promising therapeutic target.
  5. Glutathione Dynamics in the Tumor Microenvironment: A Potential Target of Cancer Stem Cells and T Cells.
  6. One-carbon metabolism shapes T cell immunity in cancer.
  7. Regulation of anti-tumor immunity by metal ion in the tumor microenvironment.
  1. BMB Rep. 2024 Jun 26. pii: 6203. [Epub ahead of print]
    Metabolic reprogramming of the tumor microenvironment to enhance immunotherapy.
    Seon Ah Lim.
      Immunotherapy represents a promising treatment strategy for targeting various tumor types. However, the overall response rate is low due to the tumor microenvironment (TME). In the TME, numerous distinct factors actively induce immunosuppression, restricting the efficacy of anticancer immune reactions. Recently, metabolic reprogramming of tumors has been recognized for its role in modulating the tumor microenvironment to enhance immune cell responses in the TME. Furthermore, recent elucidations underscore the critical role of metabolic limitations imposed by the tumor microenvironment on the effectiveness of antitumor immune cells, guiding the development of novel immunotherapeutic approaches. Hence, achieving a comprehensive understanding of the metabolic requirements of both cancer and immune cells within the TME is pivotal. This insight not only aids in acknowledging the current limitations of clinical practices but also significantly shapes the trajectory of future research endeavors in the domain of cancer immunotherapy. In addition, therapeutic interventions targeting metabolic limitations have exhibited promising potential as combinatory treatments across diverse cancer types. In this review, we first discuss the metabolic barriers in the TME. Second, we explore how the immune response is regulated by metabolites. Finally, we will review the current strategy for targeting metabolism to not simply inhibit tumor growth but also enhance antitumor immune responses. Thus, we could suggest potent combination therapy for improving immunotherapy with metabolic inhibitors.
  2. Angew Chem Int Ed Engl. 2024 Jun 25. e202410241
    Nanoscale Metal-Organic Layer Reprograms Cellular Metabolism to Enhance Photodynamic Therapy and Antitumor Immunity.
    Gan Lin, Langston Tillman, Taokun Luo, Xiaomin Jiang, Yingjie Fan, Gang Liu, Wenbin Lin.
      Abnormal cancer metabolism causes hypoxia and immunosuppressive tumor microenvironment (TME), which limits the antitumor efficacy of photodynamic therapy (PDT). Herein, we report a photosensitizing nanoscale metal-organic layer (MOL) with anchored 3‑bromopyruvate (BrP), BrP@MOL, as a metabolic reprogramming agent to enhance PDT and antitumor immunity. BrP@MOL inhibited mitochondrial respiration and glycolysis to oxygenate tumors and reduce lactate production. This metabolic reprogramming enhanced reactive oxygen species generation during PDT and reshaped the immunosuppressive TME to enhance antitumor immunity. BrP@MOL-mediated PDT inhibited tumor growth by >90% with a 40% cure rate, rejected tumor re-challenge, and prevented lung metastasis. Further combination with immune checkpoint blockade potently regressed the tumors with >98% tumor inhibition and an 80% cure rate.
    Keywords:  metal-organic layers * cancer metabolism * photodynamic therapy * two-dimensional materials * antitumor immunity
    DOI:  https://doi.org/10.1002/anie.202410241
  3. Mol Oncol. 2024 Jun 22.
    Metabolic dialogues: regulators of chimeric antigen receptor T cell function in the tumor microenvironment.
    Josquin Moraly, Taisuke Kondo, Mehdi Benzaoui, Justyn DuSold, Sohan Talluri, Marie C Pouzolles, Christopher Chien, Valérie Dardalhon, Naomi Taylor.
      Tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T cells have demonstrated remarkable success in the treatment of relapsed/refractory melanoma and hematological malignancies, respectively. These treatments have marked a pivotal shift in cancer management. However, as "living drugs," their effectiveness is dependent on their ability to proliferate and persist in patients. Recent studies indicate that the mechanisms regulating these crucial functions, as well as the T cell's differentiation state, are conditioned by metabolic shifts and the distinct utilization of metabolic pathways. These metabolic shifts, conditioned by nutrient availability as well as cell surface expression of metabolite transporters, are coupled to signaling pathways and the epigenetic landscape of the cell, modulating transcriptional, translational, and post-translational profiles. In this review, we discuss the processes underlying the metabolic remodeling of activated T cells, the impact of a tumor metabolic environment on T cell function, and potential metabolic-based strategies to enhance T cell immunotherapy.
    Keywords:  T cells; anti‐tumor immunotherapy; chimeric antigen receptor; immunometabolism; nutrient transporters; tumor microenvironment
    DOI:  https://doi.org/10.1002/1878-0261.13691
  4. Front Cell Dev Biol. 2024 ;12 1416472
    Glycolysis in the tumor microenvironment: a driver of cancer progression and a promising therapeutic target.
    Junpeng Zhao, Dandan Jin, Mengxiang Huang, Jie Ji, Xuebing Xu, Fei Wang, Lirong Zhou, Baijun Bao, Feng Jiang, Weisong Xu, Xiaomin Lu, Mingbing Xiao.
      Even with sufficient oxygen, tumor cells use glycolysis to obtain the energy and macromolecules they require to multiply, once thought to be a characteristic of tumor cells known as the "Warburg effect". In fact, throughout the process of carcinogenesis, immune cells and stromal cells, two major cellular constituents of the tumor microenvironment (TME), also undergo thorough metabolic reprogramming, which is typified by increased glycolysis. In this review, we provide a full-scale review of the glycolytic remodeling of several types of TME cells and show how these TME cells behave in the acidic milieu created by glucose shortage and lactate accumulation as a result of increased tumor glycolysis. Notably, we provide an overview of putative targets and inhibitors of glycolysis along with the viability of using glycolysis inhibitors in combination with immunotherapy and chemotherapy. Understanding the glycolytic situations in diverse cells within the tumor immunological milieu will aid in the creation of subsequent treatment plans.
    Keywords:  aerobic glycolysis; cancer progression; metabolic reprogramming; targeted therapy; tumor microenvironment
    DOI:  https://doi.org/10.3389/fcell.2024.1416472
  5. Int J Stem Cells. 2024 Jun 26.
    Glutathione Dynamics in the Tumor Microenvironment: A Potential Target of Cancer Stem Cells and T Cells.
    Youngjun Park, Eui Man Jeong.
      Glutathione (GSH), the main cellular antioxidant, dynamically influences tumor growth, metastasis, and resistance to therapy in the tumor microenvironment (TME), which comprises cancer cells, immune cells, stromal cells, and non-cellular components, including the extracellular matrix, metabolites, hypoxia, and acidity. Cancer stem cells (CSCs) and T cells are minor but significant cell subsets of the TME. GSH dynamics influences the fate of CSCs and T cells. Here, we explored GSH dynamics in CSCs and T cells within the TME, as well as therapeutic approaches that could target these dynamics.
    Keywords:  Cancer stem cells; Glutathione dynamics; T cells; Tumor microenvironment
    DOI:  https://doi.org/10.15283/ijsc24060
  6. Trends Endocrinol Metab. 2024 Jun 25. pii: S1043-2760(24)00160-7. [Epub ahead of print]
    One-carbon metabolism shapes T cell immunity in cancer.
    Yajing Qiu, Ermei Xie, Haipeng Xu, Hongcheng Cheng, Guideng Li.
      One-carbon metabolism (1CM), comprising folate metabolism and methionine metabolism, serves as an important mechanism for cellular energy provision and the production of vital signaling molecules, including single-carbon moieties. Its regulation is instrumental in sustaining the proliferation of cancer cells and facilitating metastasis; in addition, recent research has shed light on its impact on the efficacy of T cell-mediated immunotherapy. In this review, we consolidate current insights into how 1CM affects T cell activation, differentiation, and functionality. Furthermore, we delve into the strategies for modulating 1CM in both T cells and tumor cells to enhance the efficacy of adoptively transferred T cells, overcome metabolic challenges in the tumor microenvironment (TME), and maximize the benefits of T cell-mediated immunotherapy.
    Keywords:  One-carbon metabolism; T cell fate; T cell-mediated immunotherapy; folate cycle; methionine cycle
    DOI:  https://doi.org/10.1016/j.tem.2024.05.010
  7. Front Immunol. 2024 ;15 1379365
    Regulation of anti-tumor immunity by metal ion in the tumor microenvironment.
    Yaoxin Gao, Shasha Liu, Yifan Huang, Feng Li, Yi Zhang.
      Metal ions play an essential role in regulating the functions of immune cells by transmitting intracellular and extracellular signals in tumor microenvironment (TME). Among these immune cells, we focused on the impact of metal ions on T cells because they can recognize and kill cancer cells and play an important role in immune-based cancer treatment. Metal ions are often used in nanomedicines for tumor immunotherapy. In this review, we discuss seven metal ions related to anti-tumor immunity, elucidate their roles in immunotherapy, and provide novel insights into tumor immunotherapy and clinical applications.
    Keywords:  T cells; metal ions; nanomedicines; tumor immunotherapy; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2024.1379365
This page is being maintained by Thomas Krichel. It was last updated on 2025‒01‒26 at 1:54.