Class II transactivator-induced MHC class II expression in pancreatic cancer cells leads to tumor rejection and a specific antitumor memory response
CR Ekkirala, P Cappello, RS Accolla, M Giovarelli… - Pancreas, 2014 - journals.lww.com
CR Ekkirala, P Cappello, RS Accolla, M Giovarelli, I Romero, C Garrido, AM Garcia-Lora…
Pancreas, 2014•journals.lww.comObjectives 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 …
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 …
Abstract
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.
Lippincott Williams & Wilkins