Dominant negative TGF-ß receptor type II in T lymphocytes promotes anti-tumor immunity by modulating T cell subsets and enhancing CTL responses.
Biomed Pharmacother
; 148: 112754, 2022 Apr.
Article
en En
| MEDLINE
| ID: mdl-35228061
ABSTRACT
Transforming growth factor-ß (TGF-ß) is a multifunctional regulatory cytokine that maintains tolerance in the immune system by regulating the proliferation, differentiation and survival of lymphocytes. TGF-ß blockade therapy for cancer has achieved some results but shows limited efficacy and side effects because these drugs are not selective and act on various types of cells throughout the body. We demonstrate here that dominant negative TGF-ß receptor type II specifically targeting T cells decreases tumor load in tumor-bearing mice. In addition, the dominant negative TGF-ß receptor type II promotes the proliferation and differentiation of T cells and increases the expression of T-bet, which in turn promotes the secretion of granzyme A, granzyme B, perforin and IFN-γ secreted by T cells, and enhances the cytotoxicity and anti-tumor effects of T cells. Moreover, we also found that dominant negative TGF-ß receptor type II reduces the proportion of regulatory T cells (Tregs) in tumor tissue and spleen of tumor-bearing mice. Co-culture experiments with T cells and tumor cells revealed that dominant negative TGF-ß receptor type II inhibited tumor cell proliferation and increased apoptosis. Our results indicate that specifically inhibiting TGF-ß receptor type II in T cells increases anti-tumor immunity and has a strong therapeutic potential.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Subgrupos de Linfocitos T
/
Factor de Crecimiento Transformador beta
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Receptor Tipo II de Factor de Crecimiento Transformador beta
/
Neoplasias
Límite:
Animals
Idioma:
En
Revista:
Biomed Pharmacother
Año:
2022
Tipo del documento:
Article
País de afiliación:
China