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In vitro conditioned “early” but not “late” effector CD8 + T cells benefit from transient lymphopenia resulting in enhanced anti‐tumor activity
Author(s) -
DiazMontero C. Marcela,
ALKhami Amir,
Naga Osama,
Cole David,
Salem Mohamed
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1077.20
Subject(s) - priming (agriculture) , adoptive cell transfer , cd8 , cytotoxic t cell , in vitro , biology , effector , immunology , adoptive immunotherapy , cancer research , microbiology and biotechnology , antigen , biochemistry , botany , germination
A limitation of adoptive transfer therapy for cancer is the inability of transferred cells to persist. Temporary removal of endogenous lymphocytes increases the survival of transferred cells. The mechanisms behind the beneficial effects of lymphodepletion are starting to emerge; however, less is known about the impact of the phenotypic characteristics of the transferred cells on their ability to benefit from lymphodepletion. We have shown that in vitro priming of CD8+ T cells in the presence of IL‐12 promotes the generation of a subpopulation with an “early activated” phenotype (TEA). Under lymphoreplete conditions, TEAIL‐12 show enhanced survival and anti‐tumor activity when compared to TEAsham. In this study, we show that the anti‐tumor activity of TEAIL‐12 can be further enhanced after transfer into lymphopenic hosts resulting in long term regression of B16 tumors. The significance of these findings relies on the fact that tumor regression in this model is only achieved temporarly. Survival of transferred cells was dependent on their stage of differentiation. In vitro culture of TEAIL‐12 for additional 4 days abrogated their ability to survive under lymphopenic conditions. Our results suggest that long lasting anti‐tumor immunity after adoptive cell transfer could be achieved by utilizing a “fitted” T cell subtype and by promoting its survival and optimal differentiation in vivo through lymphodepletion.