Chronic lymphocytic leukemia (CLL) cells genetically modified to express B7-1, ICAM-1, and LFA-3 confer APC capacity to T cells from CLL patients |
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Authors: | Mary T Litzinger Kenneth A Foon Helen Sabzevari Kwong-Yok Tsang Jeffrey Schlom Claudia Palena |
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Institution: | (1) Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 8B09, MSC 1750, Bethesda, MD 20892, USA;(2) Division of Hematology/Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA |
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Abstract: | In chronic lymphocytic leukemia (CLL), malignant B cells and nonmalignant T cells exhibit dysfunction. We previously demonstrated
that infection of CLL cells with modified vaccinia Ankara (MVA) expressing the costimulatory molecules B7-1, ICAM-1, and LFA-3
(designated TRICOM) increased expression of these costimulatory molecules on the surface of CLL cells and thus augmented their
antigen-presenting capability. Here, we evaluate the effect of MVA-TRICOM-modified CLL cells on T cells. Following incubation
with irradiated MVA-TRICOM-modified CLL cells, allogeneic and autologous CD4+ and CD8+ T cells expressed significantly higher levels of B7-1, ICAM-1, and LFA-3. We show that this increase was the result of physical
acquisition from the antigen-presenting cells (APCs), and that purified T cells that acquired costimulatory molecules from
MVA-TRICOM-modified CLL cells were able to stimulate the proliferation of untreated T cells. These results demonstrate for
the first time that T cells from CLL patients can acquire multiple costimulatory molecules from autologous CLL cells and can
then act as APCs themselves. Given the immunodeficiencies characteristic of CLL, enhancing the antigen-presenting function
of CLL cells and T cells simultaneously could be a distinct advantage in the effort to elicit antitumor immune responses.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
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Keywords: | CLL T cells Acquisition Costimulation Immunotherapy |
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