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The reverse signals of costimulatory molecule B7‐H1 negatively regulate memory CD8 T cell function in tumor immunity
Author(s) -
Dong Haidong,
Fulko Vesna,
Harris Kimberley,
Frigola Xavier,
Liu Xin
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.22.2_supplement.523
Subject(s) - cytotoxic t cell , degranulation , cd8 , ctl* , t cell , immunology , biology , microbiology and biotechnology , antigen , cancer research , immune system , in vitro , receptor , biochemistry
The expression of B7‐H1 on tumor infiltrating lymphocytes usually correlates with poor prognosis in cancer patients. It has also been observed that B7‐H1 can deliver signals into T cells, and therefore we hypothesized that B7‐H1 on T cells reduces T cell‐mediated anti‐tumor immunity. B7‐H1 knockout (KO) mice, when compared to their WT counterparts, have increased numbers of CD8 T cells with memory effector phenotype, the population of T cells that quickly respond upon antigen restimulation. In addition, B7‐H1 KO CD8 T cells proliferate more rapidly during homeostatic expansion. Once activated, these cells exhibit improved CTL function, as demonstrated by increased degranulation and IFN‐gamma production. Blocking the B7‐H1/PD‐1 pathway not only improved the CTL function of CD8 T cells when mixed with PD‐1+ tumors in vitro but also improved their ability to reject established tumors in vivo. This novel functional role for B7‐H1 on CD8 T cells provides us with a new approach to manipulate anti‐tumor T cell response and to improve current tumor immunotherapy. (This work is funded by Mayo Foundation).