Gene expression patterns in CD4+ peripheral blood cells in healthy subjects and stage IV melanoma patients

Sara J. Felts, Virginia P. Van Keulen, Adam D. Scheid, Kathleen S. Allen, Renee K. Bradshaw, Jin Jen, Tobias Peikert, Sumit Middha, Yuji Zhang, Matthew S. Block, Svetomir N. Markovic, Larry R. Pease

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1437-1447
Number of pages11
JournalCancer Immunology Immunotherapy
Volume64
Issue number11
DOIs
StatePublished - Aug 6 2015
Externally publishedYes

Fingerprint

Melanoma
Blood Cells
Healthy Volunteers
Gene Expression
Genes
Neoplasm Genes
Gene Expression Profiling
Transcriptome
Individuality
Immune System
Patient Care
Lymph Nodes
Therapeutics
Neoplasms

Keywords

  • Gene expression
  • Immune response
  • RNAseq
  • Transcriptome

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

Felts, S. J., Van Keulen, V. P., Scheid, A. D., Allen, K. S., Bradshaw, R. K., Jen, J., ... Pease, L. R. (2015). Gene expression patterns in CD4+ peripheral blood cells in healthy subjects and stage IV melanoma patients. Cancer Immunology Immunotherapy, 64(11), 1437-1447. https://doi.org/10.1007/s00262-015-1745-x

Gene expression patterns in CD4+ peripheral blood cells in healthy subjects and stage IV melanoma patients. / Felts, Sara J.; Van Keulen, Virginia P.; Scheid, Adam D.; Allen, Kathleen S.; Bradshaw, Renee K.; Jen, Jin; Peikert, Tobias; Middha, Sumit; Zhang, Yuji; Block, Matthew S.; Markovic, Svetomir N.; Pease, Larry R.

In: Cancer Immunology Immunotherapy, Vol. 64, No. 11, 06.08.2015, p. 1437-1447.

Research output: Contribution to journalArticle

Felts, SJ, Van Keulen, VP, Scheid, AD, Allen, KS, Bradshaw, RK, Jen, J, Peikert, T, Middha, S, Zhang, Y, Block, MS, Markovic, SN & Pease, LR 2015, 'Gene expression patterns in CD4+ peripheral blood cells in healthy subjects and stage IV melanoma patients', Cancer Immunology Immunotherapy, vol. 64, no. 11, pp. 1437-1447. https://doi.org/10.1007/s00262-015-1745-x
Felts, Sara J. ; Van Keulen, Virginia P. ; Scheid, Adam D. ; Allen, Kathleen S. ; Bradshaw, Renee K. ; Jen, Jin ; Peikert, Tobias ; Middha, Sumit ; Zhang, Yuji ; Block, Matthew S. ; Markovic, Svetomir N. ; Pease, Larry R. / Gene expression patterns in CD4+ peripheral blood cells in healthy subjects and stage IV melanoma patients. In: Cancer Immunology Immunotherapy. 2015 ; Vol. 64, No. 11. pp. 1437-1447.
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