Repertoire enhancement with adoptively transferred female lymphocytes controls the growth of pre-implanted murine prostate cancer Journal Article

   

Authors:	Jenq, R. R.; Curran, M. A.; Goldberg, G. L.; Liu, C.; Allison, J. P.; van den Brink, M. R. M.
Article 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. 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. © 2012 Jenq et al.
Keywords:	adult; controlled study; nonhuman; methodology; adenocarcinoma; antigen expression; cd8+ t lymphocyte; cd8-positive t-lymphocytes; animal cell; mouse; animal; animals; mice; mus; animal experiment; animal model; transplantation; tumor antigen; animalia; prostatic neoplasms; dead box protein; dead-box rna helicases; immunological tolerance; regulatory t lymphocyte; immunology; nonmyeloablative conditioning; whole body radiation; antigens, neoplasm; prostate tumor; major histocompatibility antigen class 2; cd4+ t lymphocyte; cd4-positive t-lymphocytes; graft versus host reaction; murinae; adoptive transfer; sex difference; prostate adenocarcinoma; neoplasm transplantation; cancer control; sex factors; graft vs host disease; tumor rejection; chromosome protein; graft versus leukemia effect; adoptive immunotherapy; immunotherapy, adoptive; t lymphocyte activation; carcinoma cell; lymphocyte count; interleukin 2 receptor alpha; whole-body irradiation; major histocompatibility antigen class 1; cancer transplantation; y chromosome; lymphocyte transfer; allogeneic restriction; ddx3y protein, mouse
Journal Title:	PLoS ONE
Volume:	7
Issue:	4
ISSN:	1932-6203
Publisher:	Public Library of Science
Date Published:	2012-01-01
Start Page:	e35222
Language:	English
DOI:	10.1371/journal.pone.0035222
PROVIDER:	scopus
PMCID:	PMC3320876
PUBMED:	22493742
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84859498754&partnerID=40&md5=845dc32693b0fc0615994ff64afa79a4
Notes:	--- - "Export Date: 1 May 2012" - "Source: Scopus"

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