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Modulation of cancer-specific immune responses by amino acid degrading enzymes

Journal

IMMUNOTHERAPY
Volume 9, Issue 1, Pages 83-97

Publisher

FUTURE MEDICINE LTD
DOI: 10.2217/imt-2016-0118

Keywords

arginase; immunosuppression; indoleamine 2,3-dioxygenase; tryptophan 2,3-dioxygenase; tumor microenvironment

Categories

Funding

  1. MRC [G1000800, MC_UU_12010/1] Funding Source: UKRI
  2. Cancer Research UK [17722] Funding Source: researchfish
  3. Medical Research Council [1239050, G1000800e] Funding Source: researchfish
  4. Medical Research Council [G1000800, MC_UU_12010/1] Funding Source: Medline

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To evade immune destruction, tumors exploit a wide range of immune escape mechanisms, including the induction of an immunosuppressive tumor microenvironment. This is mediated, in part, by amino acid degrading enzymes indoleamine 2,3-dioxygenase, tryptophan 2,3-dioxygenase, arginase 1 and arginase 2, which have emerged as key players in the regulation of tumor-induced immune tolerance. Here we describe how the expression of tryptophan-and argininedegrading enzymes by tumor and tumor-infiltrating cells can hamper cancer-specific immune responses, and discuss how this knowledge is being exploited to develop new strategies for cancer immunotherapy.

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