Mechanism Of Tumor Cells Derived Microparticles Mediated Antitumor Immune Response

【Objectives】Microparticles, ranging from100nm-1000nm in diameter, are plasmamembrane-derived vesicles that shed from stimulated or apoptotic cells. They can bereleased by almost all the nucleated cells. Microparticles are now thought to playpivotal roles in inflammation and tumor metastasis by intercellular transfer ofbioactive molecules such as cytokine, mRNA and miRNA. Tumor cells derivedmicroparticles (t-MPs) carry tumor antigens, however, it is as yet unknown whethert-MPs can be used as tumor vaccines. This study is to explore a new way of tumorvaccine eliciting protective immune responses through tumor derived microparticles.【Methods】1. Tumor cells derived microparticles (t-MPs) were utilized as preventivevaccine to provoke mice, and tumor growth was observed;2. Nude mice model andCD4+T cells, CD8+T cells or NK cells depletion model were usd to detect t-MPseliciting patterns of immune responses.3. Mice were treated with t-MPs throughfoot-pad immunization to determine the uptake of t-MPs by DCs. The size, cell types,cell number and cell phenotypes of draining lymph nodes were studied respectively.4.Uptake of t-MPs by bone marrow derived dendritic cells(BMDCs), and maturationand activation of BMDCs were studied in vitro after the incubation of BMDCs andt-MPs. T cell proliferation was explored after being treated with t-MPs.【Results】1.Tumor incidence and growth were greatly inhibited in t-MPs treated mice;2.Pre-treatment of t-MPs was not able to prevent nude mice from tumor growth; CD4+or CD8+T cell depletion enhances tumor growth in t-MPs immunized mice but therewas no difference observed by NK cell depletion;3. PKH67positive DCs weremeasured in draining lymph nodes12h after injection of PKH67labeling t-MPs and the t-MPs-containing DCs was increased at24h. Hyperplasia of draining lymph nodeswas significantly after t-MPs immunization, and the number of total lymphocytes,CD4+T cells, CD8+T cells and DCs subsets all increased. Upregulation of CD80andMHCII of the DCs, compared with the control group was observed.4. BMDCs canefficiently uptake t-MPs in2h, and were activated48h after incubation with t-MPs.BMDCs activated and expanded T cell together with t-MPs,whereas t-MPs alone orimmature BMDCs did not.【Conclusion】Tumor derived microparticles are vectors that carrying tumor antigens,and could induce T cell dependent immune response, thus inhibit the tumor growth;DCs became activated and maturated after uptaking t-MPs, and t-MPs-loaded DCscould be used as therapeutic tumor vaccine for the treatment of cancer patientindividually.