Immunogenic autophagic defecants from photodynamic treated melanoma cells

• Main Authors: Yen Fu Lin, 林彥甫
• Other Authors: T. S. Wu
• Format: Others
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/02430050252572875795

碩士 === 長庚大學 === 生物醫學研究所 === 98 === Abstract Photodynamic therapy (PDT) was developed to clinically treat neoplasia. In PDT, the uptake of a photoreactive drug (photosensitizer) in combination with laser treatment results in apoptotic or autophagic cell death of targeted tumor cells. In contrast to direct tumor localization, we previously demonstrated that mice immunized with the lysate derived from B16F10 melanoma treated orderly by PDT and starvation (PLS) also generated tumor immunosurveillance. By electron microscopy, we observed the formation of autophagy as well as simultaneous exocytosis of autophagic derived defecants (ADD) during PLS. Results from confocal microscopy demonstrated that the photosensitizer, photofrin, was initially taken up by B16F10 and later found in ADD, suggesting the effectiveness of ADD. Finally, mice subsequently immunized by ADD generated anti-tumor responses against subsequently tumors challenge. In addition, the mechanisms underlying the ADD-mediated tumor immunosurveillance was also investigated. We proposed that dendritic cells (DCs) were involved in the uptake of ADD and the subsequent induction of host immune responses against tumor. A newly defined DC subset, nature killer dendritic cells (NKDC) or interferon-producing killer DCs (IKDC) were suggestive of inducing anti-tumor responses after sensitization by tumors. By multi-color flow cytometry analysis, we first demonstrated that NKDCs (or IKDC) expressed CD11cint NK1.1hi CD45RBhigh Gr-1- PDCA-1-, phenotypically analogous to previously reported tolerogenic DCs. Reduction in this DC subset was observed in IL-15R-/- mice, which was concomitant with the reduction in serum IL-10 without alternation in the occupancy of regulatory T cells.