Modulation by IL-2 of CD70 and CD27 expression on CD8+ T cells: Importance for the therapeutic effectiveness of cell transfer immunotherapy

Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
The Journal of Immunology (Impact Factor: 5.36). 07/2006; 176(12):7726-35. DOI: 10.4049/jimmunol.176.12.7726
Source: PubMed

ABSTRACT Proper T cell function relies on the integration of signals delivered by Ag, cytokine, and costimulatory receptors. In this study, the interactions between IL-2, CD27, and its ligand CD70 and their effects on human T cell function were examined. Unstimulated CD8(+) T cells expressed relatively low levels of CD70 and high levels of CD27. Incubation in vitro with high doses of IL-2 (3,000 IU/ml) or administration of IL-2 in vivo resulted in substantial up-regulation of CD70 expression and the concomitant loss of cell surface CD27 expression on CD8(+) cells. Withdrawal of IL-2 from activated CD8(+) T cells that had been maintained in IL-2 resulted in a reversal of the expression of these two markers, whereas reciprocal changes were seen following treatment of PBMCs with IL-2. The proliferation observed in cells stimulated with IL-2 primarily occurred in a subset of the CD70(+)CD8(+) T cells that up-regulated IL-2 receptor expression but did not occur in CD70(-)CD8(+) T cells. Blocking CD70 resulted in a significant reduction of T cell proliferation induced by high-dose IL-2, indicating that the interaction of CD70 with CD27 played a direct role in T cell activation mediated by IL-2. Finally, studies conducted on tumor-infiltrating lymphocyte (TIL) samples that were administered to melanoma patients indicated that the size of the pool of CD27(+)CD8(+) T cells in bulk TILs was highly associated (p = 0.004) with the ability of these TILs to mediate tumor regression following adoptive transfer.

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    • "Finally, the approach to generate cell-mediated immunotherapy by immunization with tumor-cell vaccines is still a research area. One strategy is in the form of adoptive immunotherapy stimulating antigen-specific T lymphocytes (MHC restricted) using tumor infiltrating lymphocytes (TILs) or lymphocytes from the lymph nodes draining the tumor (in both cases a key role is played by the antigen-presenting cells [APCs]) (Huang et al 2006). The difficulty with this strategy is to obtain a relatively large amount of TILs or to expand the lymphocytes from the lymph nodes. "
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