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Front. Immunol. | doi: 10.3389/fimmu.2018.00353

Targeting Tumor Metabolism: A New Challenge to improve immunotherapy

 Soumaya Kouidhi1, 2*, Farhat Ben Ayed3 and  Amel Benammar Elgaaied4
  • 1Laboratory BVBGR, LR11ES31, Higher Institute of Biotechnology of Sidi Thabet, University of Manouba, Tunisia
  • 2Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, Tunis El Manar University, Tunisia
  • 3Association Tunisienne de Lutte Contre le Cancer, Tunisia
  • 4Laboratory of Genetics, Immunology and Human Pathology,, Faculty of Sciences of Tunis, Tunis El Manar University, Tunisia

Abstract
Currently, a marked number of clinical trials on cancer treatment have revealed the success of immunomodulatory therapies based on immune checkpoint inhibitors that activate tumor-specific T cells. However, the therapeutic efficacy of cancer immunotherapies is only restricted to a small fraction of patients. A deeper understanding of key mechanisms generating an immunosuppressive tumor microenvironment remains a major challenge for more effective anti-tumor immunity. There is a growing evidence that the tumor microenvironment supports inappropriate metabolic reprogramming that dampens T cell function, and therefore impacts the anti-tumor immune response and tumor progression. Notably, the immunosuppressive TME is characterized by a lack of crucial carbon sources critical for T cell function and increased inhibitory signals. Here, we summarize the basics of intrinsic and extrinsic metabolic remodelling and metabolic checkpoints underlying the competition between cancer and infiltrating immune cells for nutrients and metabolites. Intriguingly, the upregulation of tumor PD-L1 and CTLA-4 alters the metabolic programme of T cells and drives their exhaustion. In this context, targeting both tumor and T cell metabolism can beneficially enhance or temper immunity in an inhospitable microenvironment and markedly improve the success of immunotherapies.

Keywords: T-lymphocyte metabolism, tumor cell metabolism, Tumor Microenvironment, Immunotherapy, immune checkpoints, metabolic checkpoints.

Received: 30 Nov 2017; Accepted: 07 Feb 2018.

Edited by:

Salem Chouaib, Institut Gustave Roussy, France

Reviewed by:

Viktor Umansky, Deutsches Krebsforschungszentrum (DKFZ), Germany
Graham R. Leggatt, The University of Queensland, Australia  

Copyright: © 2018 Kouidhi, Ben Ayed and Benammar Elgaaied. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Soumaya Kouidhi, Higher Institute of Biotechnology of Sidi Thabet, University of Manouba, Laboratory BVBGR, LR11ES31, Sidi Thabet, Tunisia, soumayakouidhi@gmail.com