In:
The Journal of Immunology, The American Association of Immunologists, Vol. 186, No. 1_Supplement ( 2011-04-01), p. 156.19-156.19
Abstract:
We have conducted clinical trials of adoptive γδ T cell therapy for the treatment of esophageal, colorectal, pancreatic and non-small-cell lung cancers, and cholangiocarcinoma. Patients received ≥1x109 γδ T cells every 2 weeks. These cells had been expanded ex vivo for 14 days by culture with zoledronate (5 μM) and IL-2 (1000 IU/ml). Infused γδ T cells gradually accumulated in patients’ peripheral blood and accounted for 10% of PBMC as late as 3 months after the final injection, even without IL-2 administration in vivo. These cells maintained the ability to release cytotoxic granules (detected by CD107 assay) and produce IFN-γ. To determine the factors contributing to γδ T cell survival in vivo, we investigated their expression of receptors for common γ chain (γc) family cytokines at the time of infusion. IL-2Rβ and γc, but not IL-7Rα, IL-15Rα or IL-21R, were present on these cells, and although the IL-2Rα was upregulated at the initiation of culture, it was only very weakly expressed at the time of transfer. When γδ T cells were maintained for longer periods in culture, IL-15 but not low dose IL-2 and IL-7 supported their survival. These results suggest that tissue-specific γc-dependent signals in response to IL-15 might affect the survival and function of infused γδ T cells, and hence materially influence the success of immunotherapy.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.186.Supp.156.19
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2011
detail.hit.zdb_id:
1475085-5
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