Cancer Immunology, Immunotherapy

, Volume 63, Issue 12, pp 1329–1340

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

DOI: 10.1007/s00262-014-1605-0

Cite this article as:
Foureau, D.M., Amin, A., White, R.L. et al. Cancer Immunol Immunother (2014) 63: 1329. doi:10.1007/s00262-014-1605-0

Abstract

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.

Keywords

Melanoma Renal cell carcinoma Interleukin-2 Immune monitoring Biomarkers 

Abbreviations

CR

Complete response

Foxp3

Forkhead box P3

GEE

Generalized estimating equations

IL-2

Interleukin-2

LDH

Lactate dehydrogenase

MIATA

Minimal information about T cell assay

MMEL

Metastatic melanoma

MR

Minor response

MRCC

Metastatic renal cell carcinoma

PBMC

Peripheral mononuclear cells

PD

Progressive disease

PR

Partial response

RECIST

Response evaluation criteria in solid tumor

RT

Room temperature

SD

Stable disease

Treg

Regulatory T cell

ULN

Upper limit of normal

Supplementary material

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

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