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.

Keywords: :

• cancer stem cells
• dendritic cell
• prostate cancer
• tumor immunity
• vaccination

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

Grant sponsor: Associazione Italiana per la Ricerca sul Cancro (AIRC); Ministero della salute. Elena Jachetti has been awarded a fellowship from AIRC/FIRC. We thank Paolo Dellabona and Maria Pia Protti (San Raffaele Scientific Institute, Milan, Italy) for critical revision of the manuscript. We are indebted with Renato Longhi for peptide synthesis (CNR, Milan, Italy).

Supplementary Material

Supplementary materials may be found here:

http://www.landesbioscience.com/journals/oncoimmunology/article/24520

Notes

† These authors contributed equally to this work.