Interferon signaling patterns in peripheral blood lymphocytes may predict clinical outcome after high-dose interferon therapy in melanoma patients

Simons, DL and Lee, G and Kirkwood, JM and Lee, PP (2011) Interferon signaling patterns in peripheral blood lymphocytes may predict clinical outcome after high-dose interferon therapy in melanoma patients. Journal of Translational Medicine, 9.

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Abstract

Background: High-dose Interferon (HDI) therapy produces a clinical response and achieves relapse-free survival in 20-33% of patients with operable high risk or metastatic melanoma. However, patients may develop significant side effects frequently necessitating dose reduction or discontinuation of therapy. We recently showed that peripheral blood lymphocytes (PBL) from some melanoma patients have impaired interferon (IFN) signaling which could be restored with high concentrations of IFN. This exploratory study evaluated IFN signaling in PBL of melanoma patients to assess whether the restoration of PBL IFN signaling may predict a beneficial effect for HDI in melanoma patients.Methods: PBL from 14 melanoma patients harvested on Day 0 and Day 29 of neoadjuvant HDI induction therapy were analyzed using phosflow to assess their interferon signaling patterns through IFN-α induced phosphorylation of STAT1-Y701.Results: Patients who had a clinical response to HDI showed a lower PBL interferon signaling capacity than non-responders at baseline (Day 0). Additionally, clinical responders and patients with good long-term outcome showed a significant increase in their PBL interferon signaling from Day 0 to Day 29 compared to clinical non-responders and patients that developed metastatic disease. The differences in STAT1 activation from pre- to post- HDI treatment could distinguish between patients who were inclined to have a favorable or unfavorable outcome.Conclusion: While the sample size is small, these results suggest that interferon signaling patterns in PBL correlate with clinical responses and may predict clinical outcome after HDI in patients with melanoma. A larger confirmatory study is warranted, which may yield a novel approach to select patients for HDI therapy. © 2011 Simons et al; licensee BioMed Central Ltd.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Simons, DL Lee, G Kirkwood, JM kirkwood@pitt.edu KIRKWOOD Lee, PP
Date:	5 May 2011
Date Type:	Publication
Journal or Publication Title:	Journal of Translational Medicine
Volume:	9
DOI or Unique Handle:	10.1186/1479-5876-9-52
Schools and Programs:	School of Medicine > Medicine
Refereed:	Yes
Date Deposited:	28 Oct 2016 18:40
Last Modified:	04 Feb 2019 15:56
URI:	http://d-scholarship.pitt.edu/id/eprint/30069

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