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2017 ; 13
(5
): 3781-3786
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Enhancement of antitumor immunity by combination of anti-CTLA-4 antibody and
radioimmunotherapy through the suppression of Tregs
#MMPMID28521478
Son CH
; Bae J
; Lee HR
; Yang K
; Park YS
Oncol Lett
2017[May]; 13
(5
): 3781-3786
PMID28521478
show ga
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is expressed during cluster of
differentiation (CD)4+ T-cell activation and terminates immune responses by
interrupting CD28-enhanced activation. In addition, CTLA-4 is known to be
constitutively expressed in regulatory T-cells (Tregs) and to contribute to
immune suppression by enhancing the suppressive function of Tregs. However, the
molecular mechanisms underlying CTLA-4-mediated Treg suppression remains
incompletely understood. Furthermore, it is uncertain whether the in vivo immune
suppressive functions of CTLA-4 are mediated only by a reduction in the level of
conventional T-cell activity, or enhancement of Treg function. The present study
demonstrated that combination therapy with an anti-CTLA-4 monoclonal antibody and
dendritic cell-mediated radioimmunotherapy (IR/DC) was able to promote an
antitumor response and influence Treg function in a mouse model of lung cancer.
Cell surface markers, including CTLA-4, CD25 and CD4, were analyzed using flow
cytometry, and T-cell activities were measured using ELISPOT and cytotoxicity
assays. It was revealed that anti-CTLA-4 combined treatment with IR/DC
immunotherapy may execute a more powerful and effective anti-tumor immunity
through the inhibition of Treg function.