title: Repertoire enhancement with adoptively transferred female lymphocytes controls the growth of pre-implanted murine prostate cancer.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Immunology and Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Jenq
authors.forename: Michael A
authors.initials: MA
authors.lastname: Curran
authors.forename: Gabrielle L
authors.initials: GL
authors.lastname: Goldberg
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: James P
authors.initials: JP
authors.lastname: Allison
authors.forename: Marcel R M
authors.initials: MR
authors.lastname: van den Brink
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy*; D000328:Adult; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D053487:DEAD-box RNA Helicases / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D015778:Minor Histocompatibility Antigens; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D012737:Sex Factors; D014916:Whole-Body Irradiation
chemical_list: D000951:Antigens, Neoplasm; D015778:Minor Histocompatibility Antigens; C115600:Ddx3y protein, mouse; D053487:DEAD-box RNA Helicases