Melanoma Research Today is a free monthly online journal that collates and summarizes the latest research about Melanoma, including details on identification, causes, prevention, treatment.

Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells.

Gattinoni L, Klebanoff CA, Palmer DC, Wrzesinski C, Kerstann K, Yu Z, Finkelstein SE, Theoret MR, Rosenberg SA, Restifo NP

Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1502, USA.

T cell differentiation is a progressive process characterized by phenotypic and functional changes. By transferring tumor-specific CD8+ T cells into tumor-bearing mice at various stages of differentiation, we evaluated their efficacy for adoptive immunotherapy. We found that administration of naive and early effector T cells, in combination with active immunization and IL-2, resulted in the eradication of large, established tumors. Despite enhanced in vitro antitumor properties, more-differentiated effector T cells were less effective for in vivo tumor treatment. Several events may underlie this paradoxical phenomenon: (a) downregulation of lymphoid-homing and costimulatory molecules; (b) inability to produce IL-2 and access homeostatic cytokines; and (c) entry into a proapoptotic and replicative senescent state. While the progressive acquisition of terminal effector properties is characterized by pronounced in vitro tumor killing, in vivo T cell activation, proliferation, and survival are progressively impaired. These findings suggest that the current methodology for selecting T cells for transfer is inadequate and provide new criteria for the generation and the screening of optimal lymphocyte populations for adoptive immunotherapy.

Published 2 June 2005 in J Clin Invest, 115(6): 1616-26.
Full-text of this article is available online (may require subscription).

© 2004-2008 Melanoma Research Today. All Rights Reserved.