title: Docetaxel enhances CD3+ CD56+ cytokine-induced killer cells-mediated killing through inducing tumor cells phenotype modulation.
abstract: Pretreatment with chemotherapeutic agents could sensitize human lung adenocarcinoma cells to the lyses of cytokine-induced killer (CIK) cells, however, the mechanism still unclear. We hypothesized that chemotherapeutic agents could induced immunogenic modulation (IM) and calreticulin (CRT) expression and enhanced the cytokine-induced killer (CIK) cells-mediated killing. Here, using docetaxel, one of the most widely used cancer chemotherapeutic agents, as a model, we examined the molecular and immunogenic consequences of chemotherapeutic agent exposure in lung adenocarcinoma cell SPC-A1 cells. Our results showed that the human lung adenocarcinoma cells displayed an increased sensitization to lyses of CD3+ CD56+ CIK cells after treatment with nonlethal/sublethal doses of docetaxel in vitro. Docetaxel treatment of tumor cells did not induce ATP or high-mobility group box 1 (HMGB1) secretion, or cell death. However, calreticulin (CRT) exposure was observed. Enhanced killing by CIK cells was mediated largely by CRT membrane translocation, as determined by functional knockdown of CRT, or CRT blocking antibody. This study provides evidence that the pretreatment with chemotherapeutic agents can sensitize tumor cells to the lyses of CD3+ CD56+ CIK cells in vitro through inducing immunogenic modulation and upregulating in target cells.
authors: College of Pharmacy, Jilin University, 130021 Changchun, China.
authors: WenJia
authors: W
authors: Wang
authors: Clinical medicine of Yanbian University, 133000 Yanbian, China.
authors: SiHao
authors: S
authors: Qin
authors: Institute of Frontier Medical Science of Jilin University, 1163, Xin Min Street, 130021 Changchun, China. Electronic address: ZhaoL1163@126.com.
authors: Lei
authors: L
authors: Zhao
mesh_terms: D017252:CD3 Complex / Q000378:metabolism*; D019002:CD56 Antigen / Q000378:metabolism*; D037282:Calreticulin / Q000378:metabolism; D045744:Cell Line, Tumor; D055612:Cytokine-Induced Killer Cells / Q000166:cytology* / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D000077143:Docetaxel; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007700:Kinetics; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology*; D010641:Phenotype; D043823:Taxoids / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D017252:CD3 Complex; D019002:CD56 Antigen; D037282:Calreticulin; D043823:Taxoids; D018799:Intercellular Adhesion Molecule-1; D000077143:Docetaxel
keywords: Calreticulin; Cytokine-induced killer cells; Docetaxel; Immunogenic modulation