Abstract
Analyses of NY-ESO-1-specific spontaneous immune responses in cancer patients revealed that antibody and both CD4+ and CD8+ T cell responses were induced together in cancer patients. To explore whether such integrated immune responses are also spontaneously induced for other tumor antigens, we have evaluated antibody and T cell responses against self/tumor antigen p53 in ovarian cancer patients and healthy individuals. We found that 21% (64/298) of ovarian cancer patients but no healthy donors showed specific IgG responses against wild-type p53 protein. While none of 12 patients with high titer p53 antibody showed spontaneous p53-specific CD8+ T cell responses following a single in vitro sensitization, significant p53-specific IFN-γ producing CD4+ T cells were detected in 6 patients. Surprisingly, similar levels of p53-specific CD4+ T cells but not CD8+ T cells were also detected in 5/10 seronegative cancer patients and 9/12 healthy donors. Importantly, p53-specific CD4+ T cells in healthy donors originated from a CD45RA− antigen-experienced T cell population and recognized naturally processed wild-type p53 protein. These results raise the possibility that p53-specific CD4+ T cells reflect abnormalities in p53 occurring in normal individuals and that they may play a role in processes of immunosurveillance or immunoregulation of p53-related neoplastic events.
Highlights
Increasing evidence shows that both tumor antigen-specific CD4+ and CD8+ T cells play a critical role in eradicating cancer [1,2]
21% of patients but none of the healthy individuals showed significant anti-p53 serum antibody, which was very similar to the frequency of anti-NYESO-1 antibody responses observed (21%). These frequencies of spontaneous antibody responses against p53 and NY-ESO-1 are in the range of those reported for ovarian cancer patients in various studies [29]
We report here the failure to detect in vivo-primed p53-specific CD8+ T cell responses in cancer patients with spontaneous antibodies to p53 as well as in p53seronegative patients and in healthy donors using our single in vitro sensitization protocol
Summary
Increasing evidence shows that both tumor antigen-specific CD4+ and CD8+ T cells play a critical role in eradicating cancer [1,2]. We have extensively investigated spontaneous or vaccineinduced immune responses against cancer-testis antigen NY-ESO-. Occurring NY-ESO-1-specific CD4+ and CD8+ T cell responses were typically detected only in patients who had serum antibody against NY-ESO-1, indicating that spontaneous immune responses against NY-ESO-1 in cancer patients with NY-ESO-1 expressing tumors were highly integrated [3,4]. We recently found that vaccination with MAGE-A3 protein induced integrated MAGE-A3-specific antibody, CD8+ and CD4+ T cell responses [9].
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