title: Gene expression patterns in CD4+ peripheral blood cells in healthy subjects and stage IV melanoma patients.
abstract: Melanoma patients exhibit changes in immune responsiveness in the local tumor environment, draining lymph nodes, and peripheral blood. Immune-targeting therapies are revolutionizing melanoma patient care increasingly, and studies show that patients derive clinical benefit from these newer agents. Nonetheless, predicting which patients will benefit from these costly therapies remains a challenge. In an effort to capture individual differences in immune responsiveness, we are analyzing patterns of gene expression in human peripheral blood cells using RNAseq. Focusing on CD4+ peripheral blood cells, we describe multiple categories of immune regulating genes, which are expressed in highly ordered patterns shared by cohorts of healthy subjects and stage IV melanoma patients. Despite displaying conservation in overall transcriptome structure, CD4+ peripheral blood cells from melanoma patients differ quantitatively from healthy subjects in the expression of more than 2000 genes. Moreover, 1300 differentially expressed genes are found in transcript response patterns following activation of CD4+ cells ex vivo, suggesting that widespread functional discrepancies differentiate the immune systems of healthy subjects and melanoma patients. While our analysis reveals that the transcriptome architecture characteristic of healthy subjects is maintained in cancer patients, the genes expressed differentially among individuals and across cohorts provide opportunities for understanding variable immune states as well as response potentials, thus establishing a foundation for predicting individual responses to stimuli such as immunotherapeutic agents.
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Felts
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Virginia P
authors.initials: VP
authors.lastname: Van Keulen
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Scheid
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Allen
authors.affiliation: Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Renee K
authors.initials: RK
authors.lastname: Bradshaw
authors.affiliation: Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Jen
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA.|Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Peikert
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences, Mayo Clinic College of Medicine, Rochester, MN, USA.|Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Sumit
authors.initials: S
authors.lastname: Middha
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences, Mayo Clinic College of Medicine, Rochester, MN, USA.|Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA.|Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Block
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA.|Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN, USA.|Division of Hematology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Svetomir N
authors.initials: SN
authors.lastname: Markovic
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA. pease.larry@mayo.edu.
authors.forename: Larry R
authors.initials: LR
authors.lastname: Pease
mesh_terms: D000328:Adult; D018106:CD28 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D017423:Sequence Analysis, RNA; D015398:Signal Transduction
chemical_list: D018106:CD28 Antigens; D011948:Receptors, Antigen, T-Cell
keywords: Gene expression; Immune response; RNAseq; Transcriptome