The paradigm in cancer immunotherapy has been that rejection of tumors is a function of cytotoxic T cells (CTLs). We have recently demonstrated that tumor destruction and protection from tumor challenge is not associated with the level of CTL activity. Co-injection of CpG ODN with adenovirus-based tumor vaccines (Ad5-PSA or Ad5-OVA) diminished the CD8 T cell responses however displayed a significantly higher ability to inhibit the growth of antigen-bearing tumors in CD8 T cell-dependent manner. To understand the functional importance of the fewer generated CD8 T cells, we explored the role of various molecules including FasL, perforin, granzyme B, and TRAIL, associated with tumor cell killing mechanisms. Our studies revealed that co-injection of CpG with tumor vaccine induced the expression of these molecules and the clearance of target tumor cells was independent of the role of a single molecule. On the contrary, tumor vaccine alone that induces a large number of antigen-specific CD8 T cells, target tumor cell killing was dependent on the endogenous FasL. Moreover, addition of CpG ODN induced the expression of anti-apoptotic molecules that can potentially increase the survival of CD8 T cells. Together, these studies provide evidence that co-administration of CpG ODN with a tumor vaccine generate fewer CD8 T cells \#8220;fittest for the survival\#8221; in the tumor microenvironment and can perform effective tumor cell killing utilizing multiple mechanisms. Therefore, the function of antigenic CD8 T cells is more significant than the frequency to inhibit the growth of antigen-bearing tumors. Understanding the regulatory signals programming such multiple mechanisms of tumor cell killing may help to connect the bridge between the pre-clinical and clinical studies leading to successful treatment and the cancer patient\#8217;s survival.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 365.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009