T cell activation by HSP70 vaccine requires TLR signaling and scavenger receptor SREC-1

• Published in: The Journal of immunology (1950) Vol. 183; no. 5; pp. 3092 - 3098
• Main Authors: Gong, Jianlin, Zhu, Bangmin, Murshid, Ayesha, Adachi, Hideki, Song, Baizheng, Lee, Allegra, Liu, Chunlei, Calderwood, Stuart K.
• Format: Journal Article
• Language: English
• Published: 29.07.2009
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0901235

HSP70 isolated from tumor-dendritic cell fusions (HSP70.PC-F) induces potent anti-tumor immunity and prevents growth of such tumors. In the present study, we have examined mechanisms underlying such anti-tumor activity of the HSP70.PC-F vaccine. The degree of anti-tumor immunity induced by HSP70.PC-F depended on intact TLR signaling in immunized animals, and mice in which the tlr2 and tlr4 genes were both inactivated did not respond to the vaccine. The reduced responses to HSP70.PC-F vaccine in such tlr knockout mice were restored by immunization of animals with HSP70.PC-F pulsed wild-type DC, indicating a key role for this cell type in HSP70.PC-F mediated immunity. Our studies also indicate a role for the HSP70 receptor SREC-1 in anti-tumor immunity induced by HSP70.PC-F. These two receptor types appeared functionally interdependent as indicated by the finding that tlr2 and tlr4 knockout decreases HSP70 binding in double knockout DC and reduces SREC-1 expression. In addition, TLR-dependent, tumor cell killing was suppressed by SREC-1 knockdown in DC, suggesting a significant role for this receptor in HSP70.PC-F-mediated tumor immunity.