bims-imseme Biomed News
on Immunosenescence and T cell metabolism
Issue of 2022‒04‒03
six papers selected by
Pierpaolo Ginefra
Ludwig Institute for Cancer Research

  1. Immunopharmacol Immunotoxicol. 2022 Mar 30. 1-14
      In the immunopathogenesis of systemic lupus erythematosus (SLE), there is a dysregulation of specific immune cells, including T cells. The metabolic reprogramming in T cells causes different effects. Metabolic programs are critical checkpoints in immune responses and are involved in the etiology of autoimmune disease. For instance, resting lymphocytes generate energy through oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO), whereas activated lymphocytes rapidly shift to the glycolytic pathway. Specifically, mitochondrial dysfunction, oxidative stress, abnormal metabolism (including glucose, lipid, and amino acid metabolism), and mTOR signaling are hallmarks of T lymphocyte metabolic dysfunction in SLE. Herein it is summarized how metabolic defects contribute to T cell responses in SLE, and some epigenetic alterations involved in the disease. Finally, it is shown how metabolic defects could be modified therapeutically.
    Keywords:  SLE; T cell metabolism; fatty acid oxidation; glycolysis; mTOR pathway; mitochondrial dysfunction
  2. Front Immunol. 2022 ;13 865504
    Keywords:  T-cell; metabolism; supplementation; thymus; zinc
  3. Antioxid Redox Signal. 2022 Mar 29.
      SIGNIFICANCE: Cancer immunotherapy has yielded striking anti-tumor effects in many cancers, yet the proportion of benefited patients are still limited. As key mediators of tumor suppression, CD8+ T cells are crucial for cancer immunotherapy. It has been widely appreciated that modulation of CD8+ T cell immunity could be an effective way to further improve the therapeutic benefit of immunotherapy.RECENT ADVANCES: Emerging evidence has underlined a close link between metabolism and immune functions, providing a metabolism-immune axis that is increasingly investigated for understanding CD8+ T cells regulation. On the other hand, growing findings have reported that tumors adopt multiple approaches to induce metabolic reprogramming of CD8+ T cells, leading to the compromised immunotherapy.
    CRITICAL ISSUES: CD8+ T cell metabolism in the tumor microenvironment (TME) is often adapted to diminish anti-tumor immune responses and thereby evade from immune surveillance. A better understanding of metabolic regulation of CD8+ T cells in the TME is believed to hold promise for opening a new therapeutic window to further improve the benefit of immunotherapy. We herein review the mechanistic understanding of how CD8+ T cell metabolism is reprogrammed in the TME, mainly focusing on the impact of nutrient availability and bioactive molecules secreted by surrounding cells.
    FUTURE DIRECTIONS: Future research should pay attention to tumor heterogeneity in the metabolic microenvironment and associated immune responses. It is also important to include the trending opinion of "precision medicine" in cancer immunotherapies to tailor metabolic interventions for individual patients in combination with immunotherapy treatments.
  4. J Hematol Oncol. 2022 Mar 28. 15(1): 38
      Short persistence and early exhaustion of T cells are major limits to the efficacy and broad application of immunotherapy. Exhausted T and chimeric antigen receptor (CAR)-T cells upregulate expression of genes associated with terminated T cell differentiation, aerobic glycolysis and apoptosis. Among cell exhaustion characteristics, impaired mitochondrial function and dynamics are considered hallmarks. Here, we review the mitochondrial characteristics of exhausted T cells and particularly discuss different aspects of mitochondrial metabolism and plasticity. Furthermore, we propose a novel strategy of rewiring mitochondrial metabolism to emancipate T cells from exhaustion and of targeting mitochondrial plasticity to boost CAR-T cell therapy efficacy.
    Keywords:  CAR-T cell exhaustion; Metabolism; Mitochondria; Single-cell techniques
  5. Front Immunol. 2022 ;13 840610
      T lymphocytes (T cells) are divided into two functionally different subgroups the CD4+ T helper cells (Th) and the CD8+ cytotoxic T lymphocytes (CTL). Adequate CD4 and CD8 T cell activation to proliferation, clonal expansion and effector function is crucial for efficient clearance of infection by pathogens. Failure to do so may lead to T cell exhaustion. Upon activation by antigen presenting cells, T cells undergo metabolic reprograming that support effector functions. In this review we will discuss how metabolic reprograming dictates functionality during viral infections using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human immunodeficiency virus (HIV) as examples. Moreover, we will briefly discuss T cell metabolic programs during bacterial infections exemplified by Mycobacterium tuberculosis (MT) infection.
    Keywords:  COVID-19; HIV; T cells; immunometabolism; infection; metabolism; tuberculosis