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Updated: Jul 11, 2025

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Vitamin B6 Competition in the Tumor Microenvironment Hampers Antitumor Functions of NK Cells

Chunbo He1, Dezhen Wang2, Surendra K Shukla1

  • 1Department of Oncology Science, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.

Cancer Discovery
|November 6, 2023
PubMed

Insights

Pancreatic cancer cells steal vitamin B6 (VB6), weakening immune cells. Supplementing VB6 while blocking cancer

Area of Science:

  • Immunology
  • Oncology
  • Nutritional Science

Background:

  • Nutritional factors significantly influence immune responses and antitumor immunity.
  • Tumor-induced nutritional deficiencies can impair the immune system's ability to fight cancer.
  • Pancreatic ductal adenocarcinoma (PDAC) is a complex malignancy where nutrient dynamics play a critical role.

Purpose of the Study:

  • To investigate how pancreatic ductal adenocarcinoma (PDAC) cells affect natural killer (NK) cell function through nutrient competition.
  • To explore the specific role of vitamin B6 (VB6) in NK cell-mediated antitumor immunity within the PDAC microenvironment.
  • To evaluate the therapeutic potential of VB6 supplementation combined with metabolic inhibition in PDAC models.

Main Methods:

  • Analysis of VB6 consumption by PDAC cells and its impact on the tumor microenvironment.
  • Assessment of NK cell cytotoxicity and activation in the presence of varying VB6 levels.
  • In vivo studies involving VB6 supplementation and one-carbon metabolism blockade in PDAC models.

Main Results:

  • PDAC cells actively consume VB6 to fuel their one-carbon metabolism, leading to VB6 deprivation for NK cells.
  • NK cells require VB6 for glycogenolysis, a vital energy pathway for their activation and cytotoxic function.
  • Combined VB6 supplementation and blockage of VB6-dependent one-carbon metabolism significantly reduced tumor burden in vivo.

Conclusions:

  • PDAC cells suppress NK cell antitumor immunity by competitively restricting VB6 availability.
  • Targeting VB6 metabolism presents a promising strategy to enhance NK cell function against PDAC.
  • Micronutrient dynamics are critical regulators of cancer progression and offer novel therapeutic targets.

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