Premium
Leucine metabolism as a novel approach to improve T cell performance in managing cancer
Author(s) -
Ananieva Elitsa A,
Powell Jonathan D,
Alme Angela,
Patel Chirag,
Hutson Susan M
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.915.2
Subject(s) - immune system , leucine , t cell , cancer cell , transamination , biology , cell , cancer research , cancer , amino acid , microbiology and biotechnology , biochemistry , immunology , genetics
T cells can recognize and eliminate tumors in the same way as they recognize and destroy infectious agents. There are a number of mechanisms by which tumors may evade or silence the immune response. Depriving T cells of amino acids mitigates T cell function and allows tumors to evade the immune response. We studied the impact of the branched‐chain amino acid, leucine, and its degrading enzyme, the cytosolic branched‐chain aminotransferase (BCATc) on T cell activation as a novel approach to improve T cell performance in managing cancer. Our results showed that leucine was required for T cell activation and proliferation and its depletion promoted T cell tolerance. BCATc transcripts were up‐regulated in tolerant T cells that are unable to provide a productive immune response. We observed a 15‐ fold increase in BCATc protein levels, a 13‐fold increase in BCATc activity and 6‐fold increase in leucine transamination in tolerant T cells. Moreover, BCATc was up‐regulated in prostate cancer‐infiltrating regulatory T cells known to suppress the anti‐tumor immune response. Our results indicate that leucine is a critical factor for T cell activation while BCATc is a new candidate for an immunosuppressive enzyme that may represent a novel means by which tumors evade the immune response. In as much as inhibitors of BCATc are available, our study may provide novel targets for cancer vaccines. Research support, NIH/NIDDK (R01DK081563).