Gene expression profile of peripheral blood lymphocytes from renal cell carcinoma patients treated with IL-2, Interferon-α and dendritic cell vaccine
Figure S1. Supervised hierarchical clustering analysis for T-cell and B-cell receptor associated genes of all arrays was performed. (1.377Mb)
Figure S2. Genes that were differentially regulated between mRCC patients pre and post-treatment (based on p<0.05, logFC >1,4) were selected for clustering analysis that is displayed as a heatmap. (868.7Kb)
Figure S3. Supervised hierarchical clustering of responding versus non-responding patients (based on p<0.05, logFC >1,4) is displayed as a heatmap for pre-treatment (3A) and post-treatment (3B) PBLs. No distinct clustering of the two groups occurs. (852.5Kb)
Figure S4. Comparison of treatment related changes in gene expression for responding versus non-responding patients (POST minus PRE) and analysis with IPA. (825.4Kb)
Figure S5. Peripheral blood serum concentrations for the cytokine Interferon inducible factor 10, IP-10 for healthy controls and mRCC patients PRE and POST treatment as a group and split based on response (n: 5 healthy controls, 8 mRCC: 4 R PRE, 4 NR PRE, 4 R POST, 4 NR POST). (385.3Kb)
Figure S6. Correlation between the Fold Changes of 132 RCC-associated transcripts identified in PBMCs by Twine et al (1), and the corresponding fold change for our PBL based data set. (1.544Mb)
Cote, Anik L.
Hampton, Thomas H.
Tomlinson, Craig R.
Fisher, Jan L.
Fadul, Camilo E.
Hamilton, Joshua W.
Ernstoff, Marc S.
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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 TREG-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 TREG-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.
© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 7 (2012): e50221, doi:10.1371/journal.pone.0050221.
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