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IL15 can reverse the unresponsiveness of wilms' tumor antigen-specific CTL in patients with prostate cancer.
Clinical Cancer Research
Purpose: The Wilms" tumor antigen 1 (WT1) is overexpressed in several leukemias and solid tumors, but there is currently limited information regarding its role in prostate cancer. This study aimed to investigate WT1 expression in prostate cancer, and to determine the number and function of WT1-specific Tcells in the peripheral blood of patients. Experimental Design: Immunohistochemistry was used to assess WT1 expression in cancer tissues. Human leukocyte antigen A2 (HLA-A2) tetramers served to detect WT1-spee if icTcells, and peptide-specific stimulation was used to assessT-cell function in vitro. Results: Immunohistochemistry of tissue arrays comprising 36 cancer and 8 normal prostate samples revealed nuclear WT1 staining in 39% of cancer samples, but not in normal prostate tissues. Tetramer analysis revealed a low frequency of WT1-specific T cells in 20 of 38 HLA-A2-positive patients. In vitro stimulation with WTJ peptide plus interleukin 2(IL2) and interleukin 7 (IL7) did not lead to an accumulation of WT1-specific Tcells in any of the patient samples, although all patients were able to generate T-cell responses against Melan-A/MARTI control peptide. Stimulation with WT1 peptide in the presence of interleukin 15 (IL15), a cytokine that was shown to reverse tolerance of murine tumor-specif icTcells, was able to restore the expansion and IFNγ production of WT1-specificTcells in a subgroup of prostate cancer patients. Conclusion: The observation that IL15 can restore the function of WT1-specificTcells that were unresponsive to IL2 has implications for vaccination and immunotherapeutic strategies that aim to enhance WT1-specificTcell immunity in patients. © 2009 American Association for Cancer Research.
|Title:||IL15 can reverse the unresponsiveness of wilms' tumor antigen-specific CTL in patients with prostate cancer|
|UCL classification:||UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences
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