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Critical Reviews™ in Immunology
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ISSN Druckformat: 1040-8401
ISSN Online: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v20.i1.20
40 pages

CD4+ T Cells in Adoptive Immunotherapy and the Indirect Mechanism of Tumor Rejection

Peter A. Cohen
Center for Surgery Research, NE6-307, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
Liaomin Peng
Center for Surgery Research, FF-50, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195
Gregory E. Plautz
Center for Surgery Research, FF-50, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195
Julian A. Kim
Center for Surgery Research, FF-50, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195
David E. Weng
Center for Surgery Research, FF-50, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195
Suyu Shu
Center for Surgery Research, NE6-307, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA

ABSTRAKT

Tumor-specific CD4+ effector T cells often play a decisive role in immunologic tumor rejection, in some cases without evident co-participation of CD8+ T cells. During such CD4+ T-cell-mediated rejection there is often no delectable direct contact between T cells and tumor cells. Optimally prepared, adoptively transferred CD4+ T cells can reject established tumors with great efficiency even when targeted tumor cells express no MHC Class II molecules, implying that recognition of tumor antigen (Ag) occurs via MHC Class II-expressing host antigen-presenting cells (APC) within the tumor. Because consequent rejection also excludes Ag-specific contact between CD4+ T cells and MHC Class IIneg tumor cells, the most critical CD4+ T-cell-mediated event is likely cytokine release, resulting in an accumulation and activation of accessory cells such as tumoricidal macrophages and lymphokine-activated killer cells. Although such an indirect rejection mechanism may appear antithetical to popular strategies centered on CD8+ cytotoxic T cells (CTL), current evidence suggests that even CD8+ T-cell-mediated recognition/rejection often bypasses direct tumor cell contact and is largely cytokine mediated. While CTL are likely to participate prominently in many models of tumor rejection, indirect mechanisms of recognition/ rejection have the theoretical advantage of remaining operative even when individual tumor cells evade direct contact by down-regulating MHC and/or Ag expression


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