bims-mecami 2023-11-26 papers

Issue of 2023–11–26
five papers selected by
Oltea Sampetrean, Keio University

Biochim Biophys Acta Rev Cancer. 2023 Nov 20. pii: S0304-419X(23)00171-3. [Epub ahead of print] 189022

Hurdle or thruster: Glucose metabolism of T cells in anti-tumour immunity.

Sirui Zhang, Xiaozhen Zhang, Hanshen Yang, Tingbo Liang, Xueli Bai.

Glucose metabolism is essential for the activation, differentiation and function of T cells and proper glucose metabolism is required to maintain effective T cell immunity. Dysregulation of glucose metabolism is a hallmark of cancer, and the tumour microenvironment (TME2) can create metabolic barriers in T cells that inhibit their anti-tumour immune function. Targeting glucose metabolism is a promising approach to improve the capacity of T cells in the TME. The efficacy of common immunotherapies, such as immune checkpoint inhibitors (ICIs3) and adoptive cell transfer (ACT4), can be limited by T-cell function, and the treatment itself can affect T-cell metabolism. Therefore, understanding the relationship between immunotherapy and T cell glucose metabolism helps to achieve more effective anti-tumour therapy. In this review, we provide an overview of T cell glucose metabolism and how T cell metabolic reprogramming in the TME regulates anti-tumour responses, briefly describe the metabolic patterns of T cells during ICI and ACT therapies, which suggest possible synergistic strategies.

Keywords: Adoptive cell transfer therapy; Glucose metabolism; Immune checkpoint; Metabolic reprogramming; T cell; Tumour microenvironment

DOI: https://doi.org/10.1016/j.bbcan.2023.189022

Cancer Discov. 2023 Nov 22. OF1

Vitamin B5 Supports Oncogenic Metabolism in MYC-Driven Breast Cancer.

Pantothetic acid is required for metabolic activity that supports MYC-driven breast tumor growth.

DOI: https://doi.org/10.1158/2159-8290.CD-RW2023-185

Cancer Immunol Res. 2023 Nov 21.

A metabolic axis of immune intractability.

Dominique C Hinshaw, Meet Patel, Lalita A Shevde.

Immune cells in the tumor niche robustly influence disease progression. Remarkably, in cancer, developmental pathways are re-enacted. Many parallels between immune regulation of embryonic development and immune regulation of tumor progression can be drawn, with evidence clearly supporting an immune-suppressive microenvironment in both situations. In these ecosystems, metabolic and bioenergetic circuits guide and regulate immune cell differentiation, plasticity, and functional properties of suppressive and inflammatory immune subsets. As such, there is an emerging pattern of intersection across the dynamic process of ontogeny and the ever-evolving tumor neighborhood. In this article, we focus on the convergence of immune programming during ontogeny and in the tumor microenvironment. Exemplifying dysregulation of Hedgehog (Hh) activity, a key player during ontogeny, we highlight a critical convergence of these fields and the metabolic axis of the nutrient sensing hexosamine biosynthetic pathway (HBP) that integrates glucose, glutamine, amino acids, acetyl CoA, and uridine-5'-triphosphate (UTP), culminating in the synthesis of UDP-GlcNAc, a metabolite that functions as a metabolic and bioenergetic sensor. We discuss an emerging pattern of immune regulation, orchestrated by O-GlcNAcylation of key transcriptional regulators, spurring suppressive activity of dysfunctional immune cells in the tumor microenvironment.

DOI: https://doi.org/10.1158/2326-6066.CIR-23-0433

Biomolecules. 2023 Nov 01. pii: 1604. [Epub ahead of print]13(11):

Stromal-Modulated Epithelial-to-Mesenchymal Transition in Cancer Cells.

Huda I Atiya, Grace Gorecki, Geyon L Garcia, Leonard G Frisbie, Roja Baruwal, Lan Coffman.

The ability of cancer cells to detach from the primary site and metastasize is the main cause of cancer- related death among all cancer types. Epithelial-to-mesenchymal transition (EMT) is the first event of the metastatic cascade, resulting in the loss of cell-cell adhesion and the acquisition of motile and stem-like phenotypes. A critical modulator of EMT in cancer cells is the stromal tumor microenvironment (TME), which can promote the acquisition of a mesenchymal phenotype through direct interaction with cancer cells or changes to the broader microenvironment. In this review, we will explore the role of stromal cells in modulating cancer cell EMT, with particular emphasis on the function of mesenchymal stromal/stem cells (MSCs) through the activation of EMT-inducing pathways, extra cellular matrix (ECM) remodeling, immune cell alteration, and metabolic rewiring.

Keywords: ECM remodeling; direct and indirect interaction; mesenchymal stem cells; reprograming

DOI: https://doi.org/10.3390/biom13111604

Sci Adv. 2023 11 24. 9(47): eadj6409

Longitudinal dynamics of the tumor hypoxia response: From enzyme activity to biological phenotype.

Sandy Che-Eun S Lee, Andrea Hye An Pyo, Marianne Koritzinsky.

Poor oxygenation (hypoxia) is a common spatially heterogeneous feature of human tumors. Biological responses to tumor hypoxia are orchestrated by the decreased activity of oxygen-dependent enzymes. The affinity of these enzymes for oxygen positions them along a continuum of oxygen sensing that defines their roles in launching reactive and adaptive cellular responses. These responses encompass regulation of all steps in the central dogma, with rapid perturbation of the metabolome and proteome followed by more persistent reprogramming of the transcriptome and epigenome. Core hypoxia response genes and pathways are commonly regulated at multiple inflection points, fine-tuning the dependencies on oxygen concentration and hypoxia duration. Ultimately, shifts in the activity of oxygen-sensing enzymes directly or indirectly endow cells with intrinsic hypoxia tolerance and drive processes that are associated with aggressive phenotypes in cancer including angiogenesis, migration, invasion, immune evasion, epithelial mesenchymal transition, and stemness.

DOI: https://doi.org/10.1126/sciadv.adj6409