[HTML][HTML] Tumour cell generation of inducible regulatory T-cells in multiple myeloma is contact-dependent and antigen-presenting cell-independent

S Feyler, GB Scott, C Parrish, S Jarmin, P Evans… - PloS one, 2012 - journals.plos.org
S Feyler, GB Scott, C Parrish, S Jarmin, P Evans, M Short, K McKinley, PJ Selby, G Cook
PloS one, 2012journals.plos.org
Regulatory T-cells (TReg cells) are increased in patients with multiple myeloma (MM). We
investigated whether MM cells could generate and/or expand TReg cells as a method of
immuno-surveillance avoidance. In an in vitro model, CD4+ CD25-FoxP3-T-cells co-cultured
with malignant plasma cells (primary MM cells and cell lines) induced a significant
generation of CD4+ CD25+ FoxP3+ inducible TReg cells (tTReg cells; p< 0.0001), in a
contact-dependent manner. tTReg cells were polyclonal, demonstrated a suppressive …
Regulatory T-cells (TReg cells) are increased in patients with multiple myeloma (MM). We investigated whether MM cells could generate and/or expand TReg cells as a method of immuno-surveillance avoidance. In an in vitro model, CD4+CD25-FoxP3- T-cells co-cultured with malignant plasma cells (primary MM cells and cell lines) induced a significant generation of CD4+CD25+FoxP3+ inducible TReg cells (tTReg cells; p<0.0001), in a contact-dependent manner. tTReg cells were polyclonal, demonstrated a suppressive phenotype and phenotypically, demonstrated increased FoxP3 (p = 0.0001), increased GITR (p<0.0001), increased PD1 (p = 0.003) and decreased CD62L (p = 0.007) expression compared with naturally occurring TReg cells. FACS-sorted tTReg cells differentiated into FoxP+IL-17+ and FoxP3-IL-17+ CD4+ cells upon TCR-mediated stimulation. Blocking experiments with anti-ICOS-L MoAb resulted in a significant inhibition of tTReg cell generation whereas both IL-10 & TGFβ blockade did not. MM tumour cells can directly generate functional TReg cells in a contact-dependent manner, mediated by ICOS/ICOS-L. These features suggest that tumour generation of TReg cells may contribute to evasion of immune surveillance by the host.
PLOS