Membrane-bound HSP70-engineered myeloma cell-derived exosomes stimulate more efficient CD8(+) CTL- and NK-mediated antitumour immunity than exosomes released from heat-shocked tumour cells expressing cytoplasmic HSP70.
Bottom Line: We found that EXO(HSP) were able to more efficiently stimulate maturation of DCs with up-regulation of Ia(b) , CD40, CD80 and inflammatory cytokines than EXO(HS) after overnight incubation of immature bone-marrow-derived DCs (5 × 10⁶ cells) with EXO (100 μg), respectively.We demonstrate that EXO(HSP) are able to stimulate type 1 CD4(+) helper T (Th1) cell responses, and more efficient P1A-specific CD8(+) cytotoxic T lymphocyte (CTL) responses and antitumour immunity than EXO(HS) .In addition, we further elucidate that EXO(HSP) -stimulated antitumour immunity is mediated by both P1A-specific CD8(+) CTL and non-P1A-specific natural killer (NK) responses.
Affiliation: Research Unit, Division of Health Research, Saskatchewan Cancer Agency, Department of Oncology, University of Saskatchewan, Saskatoon, Canada.Show MeSH
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Mentions: To investigate the antitumour immunity derived from EXOHSP vaccination, BALB/c mice were s.c. immunized with EXOHSP, EXOneo, EXOHS and PBS, respectively. 6 days after the immunization, the immunized mice were s.c. challenged with J558 tumour cells. As shown in Fig. 5(A), all the mice injected with PBS died of tumour within 14 days after tumour cell challenge. EXOHS and EXOneo vaccine protected four of eight (50%) and two of eight (25%) mice from tumour growth, respectively, and the rest of four or six tumour-bearing mice had significantly delayed tumour growth compared to the control group of mice treated with PBS (P < 0.05). However, EXOHSP immunization protected all eight of eight (100%) mice from tumour growth, indicating that EXOHSP expressing membrane-bound HSP70 can also induce more efficient antitumour immunity than EXOHS expressing cytoplasmic HSP70 and the control EXOneo without HSP70 expression.
Affiliation: Research Unit, Division of Health Research, Saskatchewan Cancer Agency, Department of Oncology, University of Saskatchewan, Saskatoon, Canada.