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 assess whether EXOHSP can stimulate CD4+ T-cell responses, we performed in vitro T-cell proliferation assay by using CD4+ T cells derived from EXO-immunized mouse spleens. As shown in Fig. 4(A), EXOHSP immunization could mount a more efficient CD4+ T-cell proliferation compared to that of EXOHS-immunized group (P < 0.05). To assess the type of CD4+ T-cell response, we measured the cytokine secretion of CD4+ T cells derived from EXOHSP-immunized mice by ELISA. CD4+ T cells derived from EXOHSP immunized mice secreted IL-2 (1.4 ng/ml/106 cells/24 hrs) and IFN-γ (1.1 ng/ml/106 cells/24 hrs), but not IL-4 (Fig. 4B), indicating that EXOHSP stimulate type 1 CD4+ helper T (Th1) cell responses.
Affiliation: Research Unit, Division of Health Research, Saskatchewan Cancer Agency, Department of Oncology, University of Saskatchewan, Saskatoon, Canada.