Characterization of T-cell responses against IκBα in cancer patients
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Characterization of T-cell responses against IκBα in cancer patients. / Munir, Shamaila; Frøsig, Thomas Mørch; Hansen, Morten; Svane, Inge Marie; Andersen, Mads Hald.
In: OncoImmunology, Vol. 1, No. 8, 2012, p. 1290-1296.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Characterization of T-cell responses against IκBα in cancer patients
AU - Munir, Shamaila
AU - Frøsig, Thomas Mørch
AU - Hansen, Morten
AU - Svane, Inge Marie
AU - Andersen, Mads Hald
PY - 2012
Y1 - 2012
N2 - The nuclear factor κ light chain enhancer of activated B cells (NFκB) is constitutively active in most cancers, controlling multiple cellular processes including proliferation, invasion and resistance to therapy. NFκB is primarily regulated through the association with inhibitory proteins that are known as inhibitors of NFκB (IκBs). Increased NFκB activity in tumor cells has been correlated with decrease stability of IκB proteins, in particular IκBα. In responso to a large number of stimuli, IκB proteins are degraded by the proteasome. Cytotoxic T lymphocytes (CTLs) recognize HLA-restricted antigenic peptides that are generated by proteasomal degradation in target cells. In the present study, we demonstrate the presence of naturally occurring IκBα -specific T cells in the peripheral blood of patients suffering from several unrelated tumor types, i.e., breast cancer, malignant melanoma and renal cell carcinoma, but not of healthy controls. Furthermore, we show that such IBα-specific T cells are granzyme B-releasing, cytotoxic cells. Hence, the increased proteasomal degradation of IκBα in cancer induces IκBα-specific CTLs.
AB - The nuclear factor κ light chain enhancer of activated B cells (NFκB) is constitutively active in most cancers, controlling multiple cellular processes including proliferation, invasion and resistance to therapy. NFκB is primarily regulated through the association with inhibitory proteins that are known as inhibitors of NFκB (IκBs). Increased NFκB activity in tumor cells has been correlated with decrease stability of IκB proteins, in particular IκBα. In responso to a large number of stimuli, IκB proteins are degraded by the proteasome. Cytotoxic T lymphocytes (CTLs) recognize HLA-restricted antigenic peptides that are generated by proteasomal degradation in target cells. In the present study, we demonstrate the presence of naturally occurring IκBα -specific T cells in the peripheral blood of patients suffering from several unrelated tumor types, i.e., breast cancer, malignant melanoma and renal cell carcinoma, but not of healthy controls. Furthermore, we show that such IBα-specific T cells are granzyme B-releasing, cytotoxic cells. Hence, the increased proteasomal degradation of IκBα in cancer induces IκBα-specific CTLs.
U2 - 10.4161/onci.21625
DO - 10.4161/onci.21625
M3 - Journal article
C2 - 23243592
VL - 1
SP - 1290
EP - 1296
JO - OncoImmunology
JF - OncoImmunology
SN - 2162-4011
IS - 8
ER -
ID: 48580011