Related Experiment Video

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Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
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Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells

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The CD73 immune checkpoint promotes tumor cell metabolic fitness

David Allard1,2,3, Isabelle Cousineau1,3, Eric H Ma4

  • 1Centre de Recherche du Centre Hospitalier l'Université de Montréal, Montreal, Canada.

Elife
|June 1, 2023
PubMed

Insights

CD73 enhances tumor cell metabolism and proliferation through mitochondrial respiration and aspartate biosynthesis. Targeting CD73 inhibits tumor growth and offers new combination therapy strategies.

Area of Science:

  • Oncology
  • Cancer Metabolism
  • Immunology

Background:

  • CD73, an ectonucleotidase, is overexpressed in tumors and suppresses anti-tumor immunity.
  • CD73 inhibitors are under clinical investigation, but its intrinsic effects on tumor cells are unclear.

Purpose of the Study:

  • To investigate the immune-independent role of CD73 in tumor cell metabolism and proliferation.
  • To explore potential combination therapies involving CD73 inhibition.

Main Methods:

  • Metabolomic analysis of CD73-expressing and deficient tumor cells.
  • Seahorse analysis to assess mitochondrial respiration and glycolytic reserve.
  • Assessment of tumor cell proliferation, genomic instability, and PARP activity.

Main Results:

  • CD73 significantly enhances tumor cell mitochondrial respiration and aspartate biosynthesis.
  • Restoring aspartate biosynthesis rescues proliferation in CD73-deficient tumors.
  • CD73 inhibition decreases metabolic fitness, increases genomic instability, and suppresses PARP activity.

Conclusions:

  • CD73 has a critical immune-independent function in promoting tumor cell metabolism.
  • Targeting CD73 impacts tumor cell metabolic fitness and genomic stability.
  • These findings support novel combination therapies including CD73 inhibition.
Keywords:
adenosinecancer biologyhumanimmunotherapymetabolismmouse

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