title: Prostate cancer stem cells are targets of both innate and adaptive immunity and elicit tumor-specific immune responses.
abstract: According to the cancer stem cell (CSC) theory, therapies that do not target the CSC compartment have limited, if any, chances to eradicate established tumors. While cytotoxic T lymphocytes (CTLs) have the potential to recognize and kill single neoplastic cells within a tissue, whether CSCs can be targeted by the immune system during spontaneous or vaccination-elicited responses is poorly defined. Here, we provide experimental evidence showing that CSC lines established from the prostate of transgenic adenocarcinoma of the mouse prostate (TRAMP) mice expressed prostate cancer-associated antigens, MHC Class I and II molecules as well as ligands for natural killer (NK) cell receptors. Indeed, CSC were targets for both NK cell- and CTL-mediated cytotoxicity, both in vitro and in vivo. The administration of dendritic cells pulsed with irradiated CSCs induced a tumor-specific immune response that was more robust than that induced by dendritic cells pulsed with differentiated tumor cells, delayed tumor growth in mice challenged with prostate CSCs and caused tumor regression in TRAMP mice. Thus, CSC are targeted by both innate and adaptive immune responses and might be exploited for the design of novel immunotherapeutic approaches against cancer.
authors.affiliation: Cellular Immunology Unit; PIBIC; Division of Immunology Transplantation and Infectious Disease; San Raffaele Scientific Institute; Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Jachetti
authors.forename: Stefania
authors.initials: S
authors.lastname: Mazzoleni
authors.forename: Matteo
authors.initials: M
authors.lastname: Grioni
authors.forename: Alessia
authors.initials: A
authors.lastname: Ricupito
authors.forename: Chiara
authors.initials: C
authors.lastname: Brambillasca
authors.forename: Luca
authors.initials: L
authors.lastname: Generoso
authors.forename: Arianna
authors.initials: A
authors.lastname: Calcinotto
authors.forename: Massimo
authors.initials: M
authors.lastname: Freschi
authors.forename: Anna
authors.initials: A
authors.lastname: Mondino
authors.forename: Rossella
authors.initials: R
authors.lastname: Galli
authors.forename: Matteo
authors.initials: M
authors.lastname: Bellone
keywords: cancer stem cells; dendritic cell; prostate cancer; tumor immunity; vaccination