ABSTRACT
Dendritic cell (DC) vaccine has been proved to be an effective way in cancer immunotherapy in both preclinical and clinical studies. However, limitations in DC isolation and culture have hampered its practice and promoted the development of other antigen-presenting cells (APCs) sources to fulfill that role. Our previous studies have shown that B cells loaded by tumor cell-derived autophagosomes, which we named as DRibbles (defective ribosomal products-containing blebs), could reactivate DC-induced effector T cell response. In this study, the roles of DRibble-loaded B cells in priming naïve CD8+ T cell responses and controlling tumors were investigated. We found that high-mobility group box 1 protein (HMGB1) on DRibbles was involved in DRibble-induced B cell activation, and the DRibble-triggered B cell phagocytosis via the caveolae-mediated endocytosis pathway. By using OT-I mouse-derived T cells, we demonstrated that DRibble-loaded B cells could activate specific naïve CD8+ T cells in vitro and ex vivo. In a tumor-bearing mouse model, DRibble-loaded B cells elicited systemic antitumor immunity and significantly suppressed the tumor growth. Moreover, the antitumor efficacy of DRibble-loaded B cells was enhanced when they were combined with CpG and anti-CD40 stimulation. These results suggest that DRibble-loaded B cells represent a viable and practical therapeutic vaccination strategy that might have important clinical implications for tumor immunotherapy.
Subject(s)
Autophagosomes/immunology , B-Lymphocytes/immunology , Cancer Vaccines/therapeutic use , Dendritic Cells/metabolism , Immunotherapy/methods , Neoplasms/genetics , Animals , CD8-Positive T-Lymphocytes/immunology , Cell Line, Tumor , Humans , MiceABSTRACT
The salicylic acid (SA) plays a critical role during the establishment of systemic acquired resistance (SAR) in uninfected plant tissues after localised exposure to a pathogen. Here, we studied SA in Populus tomentosa infected by the plant pathogen Botryosphaeria dothidea. The accumulation of SA and methyl salicylate (MeSA) occurred in chronological order in P. tomentosa. The SA and MeSA contents were greater at infected than uninfected sites. Additionally, a gene expression analysis indicated that SA might be accumulated by phenylalanine ammonialyase (PAL) and converted to MeSA by SA carboxyl methyltransferase (SAMT), while MeSA might convert to SA by SA-binding protein 2 (SABP2). The expressions of SAMT at infected sites and SABP2 at uninfected sites, respectively, were significantly up-regulated. Thus, SA might be converted to MeSA at infected sites and transported as a signalling molecule to uninfected sites, where it is converted to SA for SAR. Moreover, the expressions of pathogenesis-related genes PR-1, PR-2 and PR-5 in P. tomentosa were up-regulated by the B. dothidea infection. Our study determined that variations in SA and MeSA contents occur at infected and uninfected sites in poplar after pathogen infection and contributed to the remote signals for poplar SAR.