Effect of oxygen on tumor cell vaccine.

Abstract

Gliomas are the most common type of malignant brain tumor. Even with the recent progress in conventional therapies, the prognosis remains poor and development of effective immunotherapy is needed. Tumor vaccines using CpG and tumor lysate have been demonstrated as effective in glioma therapies. We hypothesized that tumor lysate grown in a physiologic 5 % O2 condition would increase immunogenicity compared to atmospheric 20 % O2 condition since glioma in situ has been demonstrated hypoxic; and hypoxic conditions can activate the danger signal to induce antitumor immunogenicity in addition to CpG. In this study, we characterized the immunogenicity of tumor lysate derived from 5 % O2 condition for the first time in comparison with 20 % O2 condition. Vaccination with lysate from 5 % O2 condition increased the numbers of several lymphocyte subsets at draining lymph nodes compared to the tumor lysate from 20 % O2 condition. Vaccination with lysate from 5 % O2 condition did not change the cytokine levels in the sera compared to the vaccination with lysate from 20 % O2. Tumor reactive antibody levels were increased with the amount of lysate used for vaccines; however, there was not a significant difference in antibody levels with 5 % O2 in comparison with 20 % O2. Lastly, using the tumor lysate from 5 % O2 condition had superior efficacy in inducing cytotoxicity against glioma compared to the tumor lysate from 20 % O2 condition. CD8+ T depletion showed that there were other cells that play a role in this cytotoxicity. Together, these data show that 5 % oxygen tumor lysate has distinct effects on immunogenicity compared to 20 % O2 lysate. These findings indicate a potential application in cancer treatment.