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Targeting Metabolism to Control Immune Responses in Cancer and Improve Checkpoint Blockade Immunotherapy

Angèle Luby1, Marie-Clotilde Alves-Guerra1

  • 1Institut Cochin, Université de Paris, INSERM, CNRS, F-75014 Paris, France.

Cancers
|December 10, 2021
PubMed

Insights

Cancer immunotherapies targeting immune checkpoints like PD1-PDL1 and CTLA4 show promise but have limited efficacy. Targeting tumor metabolism and immunometabolism offers new strategies to enhance cancer treatment effectiveness.

Area of Science:

  • Oncology
  • Immunology
  • Metabolic pathways

Background:

  • Cancer immunotherapy using immune checkpoint blockade (PD1-PDL1, CTLA4) has transformed cancer treatment.
  • However, response rates remain low for many cancer types due to the immunosuppressive tumor microenvironment (TME).
  • The TME alters immune cell function and nutrient availability, hindering anti-tumor responses.

Purpose of the Study:

  • To review metabolic pathway alterations in cancer.
  • To explore the role of immunometabolism in immune cell differentiation and function within the TME.
  • To discuss novel therapeutic strategies targeting cancer and immune cell metabolism to improve immunotherapy efficacy.

Main Methods:

  • Literature review focusing on cancer metabolism, immunometabolism, and immune checkpoint evasion.
  • Analysis of metabolic pathways regulating immune cell differentiation.
  • Examination of TME-induced metabolic stress on anti-tumor immunity.

Main Results:

  • Altered metabolic pathways are crucial for tumor growth and immune response modulation.
  • The TME imposes metabolic stress, reprogramming immune cells and limiting their anti-tumor functions.
  • Targeting metabolic pathways can enhance the efficacy of current immunotherapies.

Conclusions:

  • Understanding cancer metabolism and immunometabolism is key to overcoming immunotherapy resistance.
  • Therapeutic strategies targeting cellular energy metabolism show potential to improve cancer treatment outcomes.
  • Modulating metabolic pathways offers a promising avenue for combination therapies in cancer immunotherapy.
Keywords:
cancerimmune responseimmunotherapymetabolic drugmetabolism

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