title: Gene expression profile of peripheral blood lymphocytes from renal cell carcinoma patients treated with IL-2, interferon-α and dendritic cell vaccine.
abstract: 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.
authors.affiliation: Medical Oncology Immunotherapy Group, Section of Hematology/Oncology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, United States of America.
authors.forename: Benita
authors.initials: B
authors.lastname: Wolf
authors.forename: Adrian
authors.initials: A
authors.lastname: Schwarzer
authors.forename: Anik L
authors.initials: AL
authors.lastname: Côté
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hampton
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwaab
authors.forename: Eduardo
authors.initials: E
authors.lastname: Huarte
authors.forename: Craig R
authors.initials: CR
authors.lastname: Tomlinson
authors.forename: Jiang
authors.initials: J
authors.lastname: Gui
authors.forename: Jan L
authors.initials: JL
authors.lastname: Fisher
authors.forename: Camilo E
authors.initials: CE
authors.lastname: Fadul
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Hamilton
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
mesh_terms: D019496:Cancer Vaccines / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000235:genetics* / Q000628:therapy; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000235:genetics* / Q000628:therapy; D016131:Lymphocyte Subsets; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D016898:Interferon-alpha; D007376:Interleukin-2