title: Sequential immune monitoring in patients with melanoma and renal cell carcinoma treated with high-dose interleukin-2: immune patterns and correlation with outcome.
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.
authors.affiliation: Department of General Surgery, Carolinas Healthcare System, Charlotte, NC, 28203, USA, david.foureau@carolinas.org.
authors.forename: David M
authors.initials: DM
authors.lastname: Foureau
authors.forename: Asim
authors.initials: A
authors.lastname: Amin
authors.forename: Richard L
authors.initials: RL
authors.lastname: White
authors.forename: William
authors.initials: W
authors.lastname: Anderson
authors.forename: Chase P
authors.initials: CP
authors.lastname: Jones
authors.forename: Terry
authors.initials: T
authors.lastname: Sarantou
authors.forename: Iain H
authors.initials: IH
authors.lastname: McKillop
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Salo
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology; D015331:Cohort Studies; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D007376:Interleukin-2