The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase
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The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase. / Sørensen, Rikke Baek; Berge-Hansen, Linda; Junker, Niels; Hansen, Christina Aaen; Hadrup, Sine Reker; Schumacher, Ton N M; Svane, Inge Marie; Becker, Jürgen C; thor Straten, Per; Andersen, Mads Hald.
I: PLoS ONE, Bind 4, Nr. 9, 2009, s. e6910.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase
AU - Sørensen, Rikke Baek
AU - Berge-Hansen, Linda
AU - Junker, Niels
AU - Hansen, Christina Aaen
AU - Hadrup, Sine Reker
AU - Schumacher, Ton N M
AU - Svane, Inge Marie
AU - Becker, Jürgen C
AU - thor Straten, Per
AU - Andersen, Mads Hald
N1 - Keywords: Antigens, Neoplasm; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Dendritic Cells; Epitopes; Histocompatibility Antigens Class I; Humans; Immune System; Immunosuppressive Agents; Immunotherapy; Indoleamine-Pyrrole 2,3,-Dioxygenase; Leukocytes, Mononuclear; Models, Biological; Peptides; T-Lymphocytes
PY - 2009
Y1 - 2009
N2 - BACKGROUND: The enzyme indoleamine 2,3-dioxygenase (IDO) exerts an well established immunosuppressive function in cancer. IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance to tumor antigens. In the present study, we tested the notion whether IDO itself may be subject to immune responses. METHODS AND FINDINGS: The presence of naturally occurring IDO-specific CD8 T cells in cancer patients was determined by MHC/peptide stainings as well as ELISPOT. Antigen specific cytotoxic T lymphocytes (CTL) from the peripheral blood of cancer patients were cloned and expanded. The functional capacity of the established CTL clones was examined by chrome release assays. The study unveiled spontaneous cytotoxic T-cell reactivity against IDO in peripheral blood as well as in the tumor microenvironment of different cancer patients. We demonstrate that these IDO reactive T cells are indeed peptide specific, cytotoxic effector cells. Hence, IDO reactive T cells are able to recognize and kill tumor cells including directly isolated AML blasts as well as IDO-expressing dendritic cells, i.e. one of the major immune suppressive cell populations. CONCLUSION: IDO may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies. Furthermore, as emerging evidence suggests that IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals, IDO-based immunotherapy holds the promise to boost anti-cancer immunotherapy in general.
AB - BACKGROUND: The enzyme indoleamine 2,3-dioxygenase (IDO) exerts an well established immunosuppressive function in cancer. IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance to tumor antigens. In the present study, we tested the notion whether IDO itself may be subject to immune responses. METHODS AND FINDINGS: The presence of naturally occurring IDO-specific CD8 T cells in cancer patients was determined by MHC/peptide stainings as well as ELISPOT. Antigen specific cytotoxic T lymphocytes (CTL) from the peripheral blood of cancer patients were cloned and expanded. The functional capacity of the established CTL clones was examined by chrome release assays. The study unveiled spontaneous cytotoxic T-cell reactivity against IDO in peripheral blood as well as in the tumor microenvironment of different cancer patients. We demonstrate that these IDO reactive T cells are indeed peptide specific, cytotoxic effector cells. Hence, IDO reactive T cells are able to recognize and kill tumor cells including directly isolated AML blasts as well as IDO-expressing dendritic cells, i.e. one of the major immune suppressive cell populations. CONCLUSION: IDO may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies. Furthermore, as emerging evidence suggests that IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals, IDO-based immunotherapy holds the promise to boost anti-cancer immunotherapy in general.
U2 - 10.1371/journal.pone.0006910
DO - 10.1371/journal.pone.0006910
M3 - Journal article
C2 - 19738905
VL - 4
SP - e6910
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 9
ER -
ID: 20568793