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Metabolic Implications of Immune Checkpoint Proteins in Cancer

Elizabeth R Stirling1, Steven M Bronson2,3, Jessica D Mackert4

  • 1Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.

Cells
|January 11, 2022
PubMed

Insights

Immune checkpoint inhibitors reprogram cancer cell metabolism, impacting treatment effectiveness. Understanding these metabolic shifts is key to overcoming resistance and improving therapies.

Area of Science:

  • Immunology
  • Oncology
  • Metabolic pathways

Background:

  • Immune checkpoint proteins (e.g., PD-1/PD-L1, CTLA-4) regulate the tumor microenvironment and immune surveillance.
  • FDA-approved checkpoint inhibitors enhance anti-tumor immune responses but can also alter cellular metabolism.
  • Metabolic reprogramming affects immune cell function, cancer cell bioenergetics, and therapeutic outcomes.

Purpose of the Study:

  • To review metabolic alterations in immune and cancer cells driven by approved immune checkpoint targets.
  • To examine the influence of costimulatory receptor signaling on immunometabolism.
  • To explore the impact of diet and microbiome on immune checkpoint blockade therapy response.

Main Methods:

  • Literature review of current research on immune checkpoint proteins and metabolism.
  • Analysis of metabolic reprogramming in cancer and immune cells.
  • Investigation of factors influencing therapeutic response, including diet and microbiome.

Main Results:

  • Immune checkpoint proteins significantly influence metabolic pathways in both cancer and immune cells.
  • Metabolic reprogramming is crucial for understanding immune-related adverse events and therapeutic resistance.
  • Diet and microbiome composition can modulate the efficacy of immune checkpoint blockade therapies.

Conclusions:

  • Targeting immune checkpoint proteins induces critical metabolic changes that influence treatment success.
  • Understanding these metabolic alterations can inform the development of novel biomarkers and combination therapies.
  • Integrating metabolic strategies with immune checkpoint blockade may enhance patient responses and overcome resistance.
Keywords:
bioenergeticsdietimmune checkpoint blockadeimmune-related adverse eventsimmunometabolismmetabolism

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