Progress in dendritic cell immunotherapy: elucidating the enigma of Th-1 polarization.
The goal of harnessing the immune system to effectively eradicate neoplastic disease will require the generation of robust Th-1 type immunity and durable immunological memory against the antigenic repertoire that differentiates normal self from neoplastic self. While the literature presents a very mixed picture as to the requirement of T-cell help for the generation of both primary and memory CTL responses, there appears to be a general consensus that CD4(+) T-cell help will be required to generate durable responses against self cancer antigens that are devoid of foreign PAMPs and for which high-affinity T-cell clones have been deleted as a consequence of thymic selection. Here we comment briefly upon the characterization of an emerging regulatory pathway that enhances Th-1 polarization and CD8(+) CTL responses by a mechanism dependent upon CD40L-mediated T-cell help. Further, we speculate that the full elucidation of this mechanism might be generally useful in answering some unresolved questions regarding the initiation of Th-1 polarized responses.
Decker
William K
WK
The University of Texas MD Anderson Cancer Center, Department of Stem Cell Transplantation and Cellular Therapy, Houston, Texas 77030 , USA. wkdecker@mdanderson.org
Shpall
Elizabeth J
EJ
D000818:Animals; D023201:CD40 Ligand; D016764:Cell Polarity / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000502:physiology*; D014611:Vaccination
D023201:CD40 Ligand