BACKGROUND:In prostate cancer, genes encoding androgen-regulated, Y-chromosome-encoded, and tissue-specific antigens may all be overexpressed.
In the adult male host, however, most high affinity T cells targeting these potential tumor rejection antigens will be removed during negative selection. In contrast, the female mature T-cell repertoire should contain abundant precursors capable of recognizing these classes of prostate cancer antigens and mediating effective anti-tumor immune responses.
METHODOLOGY/PRINCIPAL FINDINGS:We find that syngeneic TRAMP-C2 prostatic adenocarcinoma cells are spontaneously rejected in female hosts. Adoptive transfer of naïve female lymphocytes to irradiated male hosts bearing pre-implanted TRAMP-C2 tumor cells slows tumor growth and mediates tumor rejection in some animals. The success of this adoptive transfer was dependent on the transfer of female CD4 T cells and independent of the presence of CD25-expressing regulatory T cells in the transferred lymphocytes. We identify in female CD4 T cells stimulated with TRAMP-C2 a dominant MHC II-restricted response to the Y-chromosome antigen DBY. Furthermore, CD8 T cell responses in female lymphocytes to the immunodominant MHC I-restricted antigen SPAS-1 are markedly increased compared to male mice. Finally, we find no exacerbation of graft-versus-host disease in either syngeneic or minor-antigen mismatched allogeneic lymphocyte adoptive transfer models by using female into male versus male into male cells.
CONCLUSIONS/SIGNIFICANCE: This study shows that adoptively transferred female lymphocytes, particularly CD4 T cells, can control the outgrowth of pre-implanted prostatic adenocarcinoma cells. This approach does not significantly worsen graft-versus-host responses suggesting it may be viable in the clinic. Further, enhancing the available immune repertoire with female-derived T cells may provide an excellent pool of prostate cancer reactive T cells for further augmentation by combination with either vaccination or immune regulatory blockade strategies.
Written by:
Jenq RR, Curran MA, Goldberg GL, Liu C, Allison JP, van den Brink MR. Are you the author?
Department of Immunology and Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
Reference: PLoS One. 2012;7(4):e35222.
doi: 10.1371/journal.pone.0035222
PubMed Abstract
PMID: 22493742