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Role of CD8 + T cell activation status in determining susceptibility to tumor‐induced immune suppression
Author(s) -
O'Sullivan Jeremy A,
McCracken James,
Lyons Gretchen,
GuevaraPatino Jose A
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.524
Subject(s) - adoptive cell transfer , cd8 , immune system , effector , t cell , cytotoxic t cell , immunology , cancer research , biology , microbiology and biotechnology , chemistry , in vitro , biochemistry
Adoptive transfer of tumor‐reactive T cells represents a potentially powerful tool in the therapy of cancer. However, clinical outcomes continue to be disappointing for unknown reasons. Here, using the B16 murine melanoma model, we show that effector CD8 + T cells, such as those generated in vitro in adoptive therapy protocols, are significantly more susceptible to tumor‐induced immune suppression than naïve T cells of the same clonotype. In contrast, in vivo ‐generated memory T cells are resistant to suppression. Depletion of CD4 + T cells or neutralization of the signaling protein transforming growth factor β (TGFβ) potently reduces levels of immune suppression. Furthermore, TGFβ receptor II (TGFβRII) is upregulated on the surface of effector T cells relative to naïve T cells, suggesting that sensitivity to TGFβ may cause the differential susceptibility to immune suppression. Our findings support a role for T cell activation status in susceptibility to tumor‐induced immune suppression and suggest that interference with TGFβ signaling in adoptively transferred effector cells or conferring memory‐like resistance to suppression may improve clinical responses to adoptive therapy. Supported by the Illinois Division of the American Cancer Society (J.A.G.) and the Cancer Research Foundation (J.A.G.).