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Pyridoxal kinase and poly(ADP-ribose) affect the immune microenvironment of locally advanced cancers

Adrien Joseph1,2,3, Juncheng Pan1,2,3, Judith Michels4

  • 1Equipe 11 labellisée par la Ligue contre le Cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Paris, France.

Oncoimmunology
|July 22, 2021
PubMed

Insights

Malignant cells evade immune responses and chemotherapy resistance by altering vitamin B6 metabolism and poly(ADP-ribose) polymerase activity. These metabolic changes reduce anti-cancer immune cells within tumors.

Area of Science:

  • Oncology
  • Immunology
  • Metabolism

Background:

  • Malignant cells develop resistance to chemotherapy and immune attack within the tumor microenvironment.
  • Previously, reduced active vitamin B6 synthesis and overactivated poly(ADP-ribose) polymerase were linked to cisplatin resistance.
  • These metabolic alterations are prognostically adverse.

Purpose of the Study:

  • To investigate the correlation between specific oncometabolic alterations and immune cell presence in the tumor microenvironment.
  • To understand how metabolic changes in cancer cells influence immune evasion.

Main Methods:

  • Analysis of tumor microenvironment composition.
  • Assessment of metabolic pathway alterations in malignant cells.
  • Correlation studies between metabolic markers and immune effector cell density.

Main Results:

  • Prognostically adverse alterations in oncometabolism were identified.
  • Reduced synthesis of active vitamin B6 (via pyridoxal kinase downregulation) and overactivation of poly(ADP-ribose) polymerase correlate with chemotherapy resistance.
  • These metabolic changes are associated with a decrease in immune effector cells within the tumor bed.

Conclusions:

  • Oncometabolic alterations, including those affecting vitamin B6 and poly(ADP-ribose) polymerase, contribute to both chemotherapy resistance and immune suppression.
  • These findings highlight a link between cancer cell metabolism and the tumor immune microenvironment.
  • Targeting these metabolic pathways may offer novel therapeutic strategies for enhancing anti-cancer immunity and overcoming resistance.
Keywords:
CD8+ T cellsTumor microenvironmentcervical cancerdendritic cellsimmune escapeimmunotherapymetabolismnon-small cell lung cancersurvivalvitamin B

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