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Suppression of T-cell responses by tumor metabolites

Katrin Singer1, Eva Gottfried, Marina Kreutz

  • 1Department of Internal Medicine 5, Hematology/Oncology, University of Erlangen, Krankenhausstrasse 12, 91054 Erlangen, Germany.

Cancer Immunology, Immunotherapy : CII
|January 18, 2011
PubMed

Insights

Tumor cells evade immune recognition by altering metabolism, depleting nutrients and creating an immunosuppressive tumor microenvironment. Targeting metabolic key players like IDO, arginase, iNOS, and LDH-A may enhance cancer immunotherapy efficacy.

Area of Science:

  • Oncology
  • Immunology
  • Metabolism

Background:

  • Tumor cells employ diverse strategies to evade T-cell-mediated immune surveillance.
  • Altered tumor cell metabolism contributes to an immunosuppressive tumor microenvironment by depleting nutrients and accumulating inhibitory metabolites.

Purpose of the Study:

  • To review the suppressive effects of key metabolic enzymes upregulated in human tumor cells on the adaptive immune system.
  • To highlight the role of metabolic alterations in tumor cells in hindering effector T-cell functions.

Main Methods:

  • Literature review focusing on the impact of tumor cell metabolism on immune escape.
  • Discussion of specific metabolic enzymes: indolamine-2,3-dioxygenase (IDO), arginase, inducible nitric oxide synthetase (iNOS), and lactate dehydrogenase (LDH)-A.

Main Results:

  • Upregulated metabolic enzymes such as IDO, arginase, iNOS, and LDH-A contribute to immune suppression within the tumor microenvironment.
  • These enzymes impair the function of effector T-cells, hindering anti-tumor immunity.

Conclusions:

  • Understanding the interplay between tumor cell metabolism and T-cell function is crucial for advancing cancer immunotherapy.
  • Targeting these metabolic pathways presents a promising therapeutic strategy to enhance the effectiveness of cancer immunotherapies.

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