Cancer Immunology, Immunotherapy

, Volume 63, Issue 12, pp 1329–1340 | Cite as

Sequential immune monitoring in patients with melanoma and renal cell carcinoma treated with high-dose interleukin-2: immune patterns and correlation with outcome

  • David M. Foureau
  • Asim Amin
  • Richard L. White
  • William Anderson
  • Chase P. Jones
  • Terry Sarantou
  • Iain H. McKillop
  • Jonathan C. Salo
Original Article


Interleukin-2 (IL-2) therapy leads to clinically relevant responses in 10–16 % of patients with metastatic melanoma (MMEL) or 10–30 % of patients with metastatic renal cell carcinoma (MRCC). To date, no biomarkers have been validated to identify patients who are likely to respond. We hypothesized that changes in T cell subset distribution in patients undergoing IL-2 therapy may correlate with treatment outcomes. Immune profiles of 64 patients (27-MMEL, 37-MRCC) were evaluated using flow cytometry at baseline, during (≥three doses) and at the end of treatment cycle (30 ± 6 h after last dose), through two courses of IL-2 therapy. Changes in distribution and phenotype of circulating CD4 and CD8 lymphocyte subsets were compared (1) based on cancer types and (2) intra-patient during the course of the IL-2 therapy. Exploratory analysis of immunologic profiles was also performed based on treatment outcome. Independent of cancer type, IL-2 led to a transient decrease of circulating effector lymphocytes, while regulatory T cells gradually increased. Interleukin-2 differentially affected a subset of CD8 T cell expressing Foxp3, depending on malignancy type. In MMEL patients, IL-2 gradually expanded circulating CD8 Foxp3+ cells; in MRCC patients, IL-2 transiently increased expression of CD103 and CCR4 homing markers. Monitoring of adaptive immune variables early on and during the course of IL-2 therapy revealed transient alterations in immune profiles, specific to MMEL and MRCC patients, related to immune balance (and ultimately response to IL-2 therapy) or T cell egress from the circulation.


Melanoma Renal cell carcinoma Interleukin-2 Immune monitoring Biomarkers 



Complete response


Forkhead box P3


Generalized estimating equations




Lactate dehydrogenase


Minimal information about T cell assay


Metastatic melanoma


Minor response


Metastatic renal cell carcinoma


Peripheral mononuclear cells


Progressive disease


Partial response


Response evaluation criteria in solid tumor


Room temperature


Stable disease


Regulatory T cell


Upper limit of normal



This study was funded in part by a seed grant from the Carolinas Healthcare Foundation, the Purple Promise Foundation to end Melanoma and the Freedland Foundation. We thank Dr. Carol Farhangfar for comments on the manuscript, Dr. H James Norton for helping with statistical analysis, Joey Armstrong and Kendall Carpenter for compiling clinical data and Patricia Hevey for semantic and syntactic corrections.

Conflict of interest

Drs. Amin and White are members of Prometheus speaker’s bureau. All other authors have no commercial or consultancy conflict of interest.

Supplementary material

262_2014_1605_MOESM1_ESM.pdf (418 kb)
Supplementary material 1 (PDF 417 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • David M. Foureau
    • 1
  • Asim Amin
    • 2
  • Richard L. White
    • 1
    • 2
  • William Anderson
    • 3
  • Chase P. Jones
    • 1
  • Terry Sarantou
    • 1
    • 2
  • Iain H. McKillop
    • 1
  • Jonathan C. Salo
    • 1
    • 2
  1. 1.Department of General SurgeryCarolinas Healthcare SystemCharlotteUSA
  2. 2.Levine Cancer InstituteCarolinas Healthcare SystemCharlotteUSA
  3. 3.Dickson Advanced Analytic GroupCarolinas Healthcare SystemCharlotteUSA

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