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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4865-4876. Prepublished online as a Blood First Edition Paper on February 6, 2007; DOI 10.1182/blood-2006-09-045245. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-09-045245v1 109/11/4865    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wang, L.-X. Articles by Plautz, G. E. Search for Related Content PubMed PubMed Citation Articles by Wang, L.-X. Articles by Plautz, G. E. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Adoptive transfer of tumor-primed, in vitro–activated, CD4+ T effector cells (TEs) combined with CD8+ TEs provides intratumoral TE proliferation and synergistic antitumor response Li-Xin Wang1, Suyu Shu1, Mary L. Disis2, and Gregory E. Plautz1 1 Center for Surgery Research, The Cleveland Clinic Foundation, Cleveland, OH; 2 Center for Translational Medicine in Women's Health, Tumor Vaccine Group, University of Washington, Seattle, WA The importance of CD4+ Th1 cells during the effector phase of the antitumor response has been overshadowed by emphasis on CD8+ cytotoxic T lymphocytes (CTLs). To determine their respective functions, we purified antigen-primed T cells from tumor-draining lymph nodes and separately activated CD4+ and CD8+ subsets in vitro. Adoptive transfer of CD4+ T effector cells (TEs) combined with CD8+ TEs provided synergistic therapy for mice bearing subcutaneous, intracranial, or advanced pulmonary metastases. CD4+ TEs augmented IFN- production by CD8+ TEs when cells were stimulated by tumor digest–containing antigen-presenting cells (APCs). CD4+ TEs infiltrated and proliferated extensively in pulmonary tumors, while also stimulating tumor antigen–specific CD8+ T cells. By contrast, CD8+ TEs showed minimal intratumoral proliferation in the absence of CD4+ cells or when systemically transferred CD4+ cells were prevented from infiltrating pulmonary tumors by pretreatment with pertussis toxin. Irradiation of CD4+ T cells immediately prior to adoptive transfer abrogated their intratumoral proliferation and direct antitumor efficacy but did not block their capacity to stimulate intratumoral CD8+ TE proliferation or tumor regression. These results highlight the importance of cross-presentation of tumor antigens during the effector phase of immunotherapy and suggest that approaches to stimulate CD4+ TE function and boost APC cross-presentation within tumors will augment cancer immunotherapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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