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2016 ; 5
(7
): e1180485
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Tumor-released autophagosomes induce IL-10-producing B cells with suppressive
activity on T lymphocytes via TLR2-MyD88-NF-?B signal pathway
#MMPMID27622036
Zhou M
; Wen Z
; Cheng F
; Ma J
; Li W
; Ren H
; Sheng Y
; Dong H
; Lu L
; Hu HM
; Wang LX
Oncoimmunology
2016[Jul]; 5
(7
): e1180485
PMID27622036
show ga
Recent studies have shown that tumor cells can release autophagosomes, which
transport a broad array of biologically active molecules with potential
modulatory effects on immune cell functions. In this study, we aimed to
investigate the role of tumor cells-released autophagosomes (i.e. TRAP) in
regulating B cell differentiation and function. TRAPs from murine tumor cell
lines were found to induce splenic B cells to differentiate into IL-10-producing
regulatory B cells (Bregs) with a distinct phenotype of CD1d(+) CD5(+), which
could potently inhibit CD8(+) and CD4(+) T cell responses in IL-10-depedent
manner both in vitro and in vivo. Notably, adoptive transfer of TRAP-induced
Bregs abrogated the immune response and antitumor effect induced by OVA-loaded DC
vaccinations in E.G7-OVA-bearing mouse model. Mechanistic studies revealed that
membrane-bound high-mobility group B1 (HMGB1) on the intact TRAPs was crucial for
inducing Breg differentiation via the activation of TLR2-MyD88-NF-?B signal
pathway in B cells. Moreover, TRAPs enriched from malignant effusions of cancer
patients could induce human B cells to differentiate into IL-10-producing B cells
with immunoregulatory functions, the frequency of which were positively
correlated with the HMGB1 levels on TRAPs. Together, our findings have
demonstrated that TRAPs promote the generation of IL-10(+) Bregs, which may
contribute to the suppression of antitumor immunity.