Gene expression patterns in CD4+ peripheral blood cells in healthy subjects and stage IV melanoma patients
| Autor: | Yuji Zhang, Renee K. Bradshaw, Larry R. Pease, Virginia P. Van Keulen, Kathleen S. Allen, Jin Jen, Sumit Middha, Tobias Peikert, Svetomir N. Markovic, Adam D. Scheid, Sara J. Felts, Matthew S. Block |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Cancer Research Immunology Receptors Antigen T-Cell Biology Article Transcriptome Immune system CD28 Antigens Gene expression medicine Humans Immunology and Allergy Melanoma Gene Neoplasm Staging Sequence Analysis RNA Gene Expression Profiling Cancer Middle Aged medicine.disease Gene expression profiling Oncology Female Ex vivo Signal Transduction |
| Zdroj: | Cancer Immunology, Immunotherapy. 64:1437-1447 |
| ISSN: | 1432-0851 0340-7004 |
| DOI: | 10.1007/s00262-015-1745-x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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