A low, non-toxic dose of paclitaxel can prevent dendritic cell-precursors from becoming tolerogenic dendritic cells with impaired functions.
Tumor infiltrating dendritic cells (TIDCs) are thought to be potent antigen-presenting cells able to activate tumor-specific cytotoxic T lymphocytes (CTLs) or tolerogenic DCs that suppress immune reaction against tumors to escape. We have recently reported that majority of these TIDCs were DEC-205(+) DCs having a cross-presenting ability of captured tumor antigens to CD8(+) T cells via class I MHC (MHC-I) molecules, nevertheless, when the TIDCs expressed down-modulated costimulatory molecules, such as CD80 and CD86, they will inhibit the priming and activation of immune effectors (Immunol. Cell Biol., 91: 545-555, 2013). Here, we show that DC-precursors (preDCs) but not the established DCs become tolerogenic DCs expressing down-regulated costimulatory molecules having low responsiveness to LPS or tumor cells, when exposed to soluble factors released from the encountered ovarian tumors in the early phase of their development. However, we found that we could reduce the secretion of those soluble factors with a low, nontoxic concentration of paclitaxel (PTX) and we could stop the preDCs to be tolerogenic DCs and maintain DC functions. These findings indicate that we could prevent the induction of tolerogenic DCs from preDCs by using low, non-toxic doses of anti-cancer drugs to establish DCs that effectively elicit tumor-specific CTLs.
Department of Microbiology and Immunology, Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo 113-8602, Japan.
Tomohiko
T
Matsuhashi
Masumi
M
Shimizu
Yasuyuki
Y
Negishi
Toshiyuki
T
Takeshita
Hidemi
H
Takahashi
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D009000:Monocytes / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000276:immunology*; D017239:Paclitaxel / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D017239:Paclitaxel