Gene expression profile of peripheral blood lymphocytes from renal cell carcinoma patients treated with IL-2, interferon-α and dendritic cell vaccine

• Published in: PloS one Vol. 7; no. 12; p. e50221
• Main Authors: Wolf, Benita, Schwarzer, Adrian, Côté, Anik L, Hampton, Thomas H, Schwaab, Thomas, Huarte, Eduardo, Tomlinson, Craig R, Gui, Jiang, Fisher, Jan L, Fadul, Camilo E, Hamilton, Joshua W, Ernstoff, Marc S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03-12-2012; Public Library of Science (PLoS)
• Subjects: Anticancer properties; B-cell receptor; Biology; Biomarkers; Blood; Cancer; Cancer therapies; Cancer Vaccines - therapeutic use; Carcinoma, Renal Cell - blood; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - therapy; Cell activation; Clinical trials; Cluster Analysis; Combined treatment; Combined vaccines; Cotton; Cotton, Norris; Cytokines; Cytokines - blood; Cytometry; Cytotoxicity; Dendritic cells; Dendritic Cells - immunology; Down-regulation; Female; Flow Cytometry; Gene expression; Gene Expression Profiling; Hematology; Humans; Immune system; Immunotherapy; Inflammation; Interferon; Interferon-alpha - therapeutic use; Interleukin 2; Interleukin-2 - therapeutic use; Kidney cancer; Kidney Neoplasms - blood; Kidney Neoplasms - genetics; Kidney Neoplasms - therapy; Ligands; Lymphocyte Subsets; Lymphocytes; Lymphocytes - metabolism; Lymphocytes B; Lymphocytes T; Male; Medical schools; Medicine; Metastases; Metastasis; Middle Aged; Oligonucleotide Array Sequence Analysis; Oncology; Patients; Peripheral blood; Real-Time Polymerase Chain Reaction; Renal cell carcinoma; Signaling; Target recognition; Vaccines; Lebanon; United States > US; New Hampshire
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0050221

Lymphocytes are a key component of the immune system and their differentiation and function are directly influenced by cancer. We examined peripheral blood lymphocyte (PBL) gene expression as a biomarker of illness and treatment effect using the Affymetrix Human Gene ST1 platform in patients with metastatic renal cell carcinoma (mRCC) who received combined treatment with IL-2, interferon-?-2a and dendritic cell vaccine. We examined gene expression, cytokine levels in patient serum and lymphocyte subsets as determined by flow cytometry (FCM). Pre-treatment PBLs from patients with mRCC exhibit a gene expression profile and serum cytokine profile consistent with inflammation and proliferation not found in healthy donors (HD). PBL gene expression from patients with mRCC showed increased mRNA of genes involved with T-cell and T(REG)-cell activation pathways, which was also reflected in lymphocyte subset distribution. Overall, PBL gene expression post-treatment (POST) was not significantly different than pre-treatment (PRE). Nevertheless, treatment related changes in gene expression (post-treatment minus pre-treatment) revealed an increased expression of T-cell and B-cell receptor signaling pathways in responding (R) patients compared to non-responding (NR) patients. In addition, we observed down-regulation of T(REG)-cell pathways post-treatment in R vs. NR patients. While exploratory in nature, this study supports the hypothesis that enhanced inflammatory cytotoxic pathways coupled with blunting of the regulatory pathways is necessary for effective anti-cancer activity associated with immune therapy. This type of analysis can potentially identify additional immune therapeutic targets in patients with mRCC.