Spontaneous presence of FOXO3-specific T cells in cancer patients
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Spontaneous presence of FOXO3-specific T cells in cancer patients. / Larsen, Stine Kiaer; Ahmad, Shamaila Munir; Idorn, Manja; Met, Özcan; Martinenaite, Evelina; Svane, Inge Marie; Straten, Per Thor; Andersen, Mads Hald.
In: OncoImmunology, Vol. 3, No. 8, e953411, 01.01.2014.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Spontaneous presence of FOXO3-specific T cells in cancer patients
AU - Larsen, Stine Kiaer
AU - Ahmad, Shamaila Munir
AU - Idorn, Manja
AU - Met, Özcan
AU - Martinenaite, Evelina
AU - Svane, Inge Marie
AU - Straten, Per Thor
AU - Andersen, Mads Hald
PY - 2014/1/1
Y1 - 2014/1/1
N2 - In the present study, we describe forkhead box O3 (FOXO3)-specific, cytotoxic CD8(+) T cells existent among peripheral-blood mononuclear cells (PBMCs) of cancer patients. FOXO3 immunogenicity appears specific, as we did not detect reactivity toward FOXO3 among T cells in healthy individuals. FOXO3 may naturally serve as a target antigen for tumor-reactive T cells as it is frequently over-expressed in cancer cells. In addition, expression of FOXO3 plays a critical role in immunosuppression mediated by tumor-associated dendritic cells (TADCs). Indeed, FOXO3-specific cytotoxic T lymphocytes (CTLs) were able to specifically recognize and kill both FOXO3-expressing cancer cells as well as dendritic cells. Thus, FOXO3 was processed and presented by HLA-A2 on the cell surface of both immune cells and cancer cells. As FOXO3 programs TADCs to become tolerogenic, FOXO3 signaling thereby comprises a significant immunosuppressive mechanism, such that FOXO3 targeting by means of specific T cells is an attractive clinical therapy to boost anticancer immunity. In addition, the natural occurrence of FOXO3-specific CTLs in the periphery suggests that these T cells hold a function in the complex network of immune regulation in cancer patients.
AB - In the present study, we describe forkhead box O3 (FOXO3)-specific, cytotoxic CD8(+) T cells existent among peripheral-blood mononuclear cells (PBMCs) of cancer patients. FOXO3 immunogenicity appears specific, as we did not detect reactivity toward FOXO3 among T cells in healthy individuals. FOXO3 may naturally serve as a target antigen for tumor-reactive T cells as it is frequently over-expressed in cancer cells. In addition, expression of FOXO3 plays a critical role in immunosuppression mediated by tumor-associated dendritic cells (TADCs). Indeed, FOXO3-specific cytotoxic T lymphocytes (CTLs) were able to specifically recognize and kill both FOXO3-expressing cancer cells as well as dendritic cells. Thus, FOXO3 was processed and presented by HLA-A2 on the cell surface of both immune cells and cancer cells. As FOXO3 programs TADCs to become tolerogenic, FOXO3 signaling thereby comprises a significant immunosuppressive mechanism, such that FOXO3 targeting by means of specific T cells is an attractive clinical therapy to boost anticancer immunity. In addition, the natural occurrence of FOXO3-specific CTLs in the periphery suggests that these T cells hold a function in the complex network of immune regulation in cancer patients.
U2 - 10.4161/21624011.2014.953411
DO - 10.4161/21624011.2014.953411
M3 - Journal article
C2 - 25960934
VL - 3
JO - OncoImmunology
JF - OncoImmunology
SN - 2162-4011
IS - 8
M1 - e953411
ER -
ID: 138817482