Stimulation of dendritic cells by DAMPs in ALA-PDT treated SCC tumor cells

Abstract

// Xiaojie Wang 1, * , Jie Ji 1, * , Haiyan Zhang 1 , Zhixia Fan 1 , Linglin Zhang 1 , Lei Shi 1 , Feifan Zhou 2 , Wei R. Chen 2, 1 , Hongwei Wang 3 , Xiuli Wang 1 1 Shanghai Skin Disease Hospital, Shanghai 200443, China 2 Biophotonics Research Laboratory, Center for Interdisciplinary Biomedical Education and Research, University of Central Oklahoma, Edmond, OK 73034, USA 3 Huadong Hospital, Fudan University, Shanghai 200040, China * These authors have contributed equally to this work Correspondence to: Xiuli Wang, e-mail: wangxiuli20150315@163.com Hongwei Wang, e-mail: hongweiwang2005@aliyun.com Keywords: danger-associated molecular patterns, 5-aminolevulinic acid mediated photodynamic therapy, squamous cell carcinoma, dendritic cells, immune responses Received: July 03, 2015      Accepted: October 04, 2015      Published: November 26, 2015 ABSTRACT Photodynamic therapy (PDT) not only kills tumor cells directly but also rapidly recruits and activates immune cells favoring the development of antitumor adaptive immunity. It is believed that Topical 5-aminolevulinic acid mediated photodynamic therapy (ALA-PDT) can induce anti-tumor immune responses through dangerous signals damage-associated molecular patterns (DAMPs). In this study, we investigated the effect of ALA-PDT induced DAMPs on immune cells. We focused on the stimulation of dendritic cells by major DAMPs, enhanced the expression of calreticulin (CRT), heat shock proteins 70 (HSP70), and high mobility group box 1 (HMGB1), either individually or in combination. We evaluated in vitro and in vivo expressions of DAMPs induced by ALA-PDT using immunohistochemistry, western blot, and ELISA in a squamous cell carcinoma (SCC) mouse model. The role of DAMPs in the maturation of DCs potentiated by ALA-PDT-treated tumor cells was detected by FACS and ELISA. Our results showed that ALA-PDT enhanced the expression of CRT, HSP70, and HMGB1. These induced DAMPs played an important part in activating DCs by PDT-treated tumor cells, including phenotypic maturation (increase of surface expression of MHC-II, CD80, and CD86) and functional maturation (enhanced capability to secrete IFN-γ and IL-12). Furthermore, injecting ALA-PDT-treated tumor cells into naïve mice resulted in complete protection against cancer cells of the same origin. Our findings indicate that ALA-PDT can increase DAMPs and enhance tumor immunogenicity, providing a promising strategy for inducing a systemic anticancer immune response.