Manipulation of glucose availability to boost cancer immunotherapies

F. Marchesi, D. Vignali, Beatrice Manini, A. Rigamonti, P. Monti

Research output: Contribution to journalArticlepeer-review

Abstract

The orchestration of T cell responses is intimately linked to the execution of metabolic processes, both in homeostasis and disease. In cancer tissues, metabolic alterations that characterize malignant transformation profoundly affect the composition of the immune microenvironment and the accomplishment of an effective anti-tumor response. The growing understanding of the metabolic regulation of immune cell function has shed light on the possibility to manipulate metabolic pathways as a strategy to improve T cell function in cancer. Among others, glucose metabolism through the glycolytic pathway is central in shaping T cell responses and emerges as an ideal target to improve cancer immunotherapy. However, metabolic manipulation requires a deep level of control over side-effects and development of biomarkers of response. Here, we summarize the metabolic control of T cell function and focus on the implications of metabolic manipulation for the design of immunotherapeutic strategies. Integrating our understanding of T cell function and metabolism will hopefully foster the forthcoming development of more effective immunotherapeutic strategies. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Original languageEnglish
Pages (from-to)1-16
Number of pages16
JournalCancers
Volume12
Issue number10
DOIs
Publication statusPublished - 2020

Keywords

  • Glucose metabolism
  • Glut1
  • Immune therapies
  • T cells
  • 3 fluoro 1,2 phenylene bis(3 hydroxybenzoic acid) 3 hydroxy benzoic acid 1,1' (3 fluoro 1,2 phenylene)ester
  • 3 hydroxybenzoic acid
  • 4 [[[[4 (1,1 dimethyl)phenyl]sulfonyl]amino]methyl] n 3 pyridinyl benzamide
  • antineoplastic agent
  • bay 876
  • benzamide derivative
  • deoxyglucose
  • glucose
  • glucose transport affecting agent
  • glucose transporter 1
  • metformin
  • n4 [1 [(4 cyanophenyl)methyl] 5 methyl 3 (trifluoromethyl) 1h pyrazol 4 yl] 7 fluoro 2,4 quinolinedicarboxamide
  • quinoline derivative
  • stf 31
  • unclassified drug
  • wzb 117
  • antineoplastic activity
  • cancer immunotherapy
  • cancer inhibition
  • cell metabolism
  • chimeric antigen receptor T-cell immunotherapy
  • drug selectivity
  • drug structure
  • drug targeting
  • glucose metabolism
  • glycolysis
  • human
  • IC50
  • immunocompetent cell
  • ketogenic diet
  • low carbohydrate diet
  • lymphocyte function
  • malignant neoplasm
  • malignant transformation
  • metabolic regulation
  • nonhuman
  • off-target effect
  • regulatory T lymphocyte
  • Review
  • T lymphocyte
  • tumor growth
  • tumor immunology
  • tumor microenvironment

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