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Abstract: Conversion of conventional T cells into T regulatory cells (Tregs) has been proposed as a potential mechanism for Treg expansion in cancer. However, this evidence is supported by in vitro or mouse model studies with no data from in vivo or human studies to support its role in enriching peripheral and tumor-infiltrating Tregs. Recent work has shown that induced FoxP3+ Tregs (iTregs) do not express Helios; an Ikaros family transcription factor. We analyzed peripheral blood samples from untreated renal cell carcinoma (RCC) patients and following interleukin (IL)-2 treatment for the expression of FoxP3 and Helios. Our work shows that expanded peripheral FoxP3+ Tregs in untreated RCC patients co-express Helios. Interestingly, IL-2 administration results in expansion of FoxP3+Helios+ natural Tregs (nTregs) significantly more than FoxP3+Helios− iTregs. Our work shows that the increased FoxP3+ Treg subpopulation in RCC patients co-express Helios, indicating that they could be derived from natural but not induced Tregs. [Copyright &y& Elsevier]

Abstract: Modest work has been performed to improve the sensitivity of residual disease detection or investigate the contribution that the immune system makes in controlling metastatic tumor growth, in particular, the frequency and biological actions of peptide-specific CD8+ T lymphocytes in limiting metastatic disease and/or maintaining remission. Fifty-three peripheral blood samples from 32 prostate cancer (PC) patients were investigated for the presence of circulating prostate-specific antigen (PSA)-expressing cells (CPECs) using a highly sensitive and specific assay combining immunomagnetic epithelial cell enrichment with nested RT-PCR of PSA mRNA. Using HLA-A2 tetramer complexes, frequency of CD8+ T cells specific for PSA-derived peptides was determined. Additionally, serum concentrations of PSA and testosterone were measured. CPECs were detected in 26% of peripheral blood samples from PC patients. CD8+ T cells specific for PSA-derived peptides were detected at low frequency in HLA-A2-positive PC patients. The correlation between these PSA-specific CD8+ T cells and residual prostate tumor cells and clinical measures was investigated. Our data suggest that frequency of PSA-specific CD8+ T cells is correlated to CPECs, but not to serum PSA level. [Copyright &y& Elsevier]