Class II transactivator-induced MHC class II expression in pancreatic cancer cells leads to tumor rejection and a specific antitumor memory response.
| Autor: | Ekkirala CR; From the *Center for Experimental Research and Medical Studies, Città della Salute e della Scienza di Torino; and †Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino; ‡Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy; §UGC Laboratorio Clinico, Hospital Universitario Virgen de las Nieves; and ∥Department of Bioquımica, Biologia Molecular e Inmunologia III, Universidad de Granada, Granada, Spain., Cappello P, Accolla RS, Giovarelli M, Romero I, Garrido C, Garcia-Lora AM, Novelli F |
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| Jazyk: | angličtina |
| Zdroj: | Pancreas [Pancreas] 2014 Oct; Vol. 43 (7), pp. 1066-72. |
| DOI: | 10.1097/MPA.0000000000000160 |
| Abstrakt: | Objectives: The loss of major histocompatibility complex (MHC) classes I and II is a well-known mechanism by which cancer cells are able to escape from immune recognition. In this study, we analyzed the expression of antigen processing and presenting molecules in 2 cell lines derived from mouse models of pancreatic ductal adenocarcinoma (PDA) and the effects of the re-expression of MHC class II on PDA rejection. Methods: The PDA cell lines were analyzed for the expression of MHC class I, II, and antigen-processing molecules by flow cytometry or polymerase chain reaction. We generated stable PDA-MHC class II transactivator (CIITA) cells and injected them into syngeneic mice. The CD4 and CD8 T-cell role was analyzed in vitro and in vivo. Results: Murine PDA cell lines were negative for MHC and antigen-processing molecules, but their expression was restored by exogenous interferon-γ. CIITA-tumor cells were rejected in 80% to 100% of injected mice, which also developed long-lasting immune memory. In vitro assays and immunohistochemical analyses revealed the recruitment of T effector cells and CD8 T cells into the tumor area. Conclusions: Overall, these data confirm that immunotherapy is a feasible therapeutic approach to recognize and target an aggressive cancer such as PDA. |
| Databáze: | MEDLINE |
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