Spontaneous presence of FOXO3-specific T cells in cancer patients

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 - 2014/8/3

Y1 - 2014/8/3

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

SN - 2162-4011

VL - 3

JO - OncoImmunology

JF - OncoImmunology

IS - 8

M1 - e953411

ER -