IL-2-Based Therapy May Compromise Treatment Outcomes for Metastatic Renal Cell Carcinoma Patients

Strategic Insights -

Scientists in Aarhus, Denmark, have found that interleukin-2 (IL-2) administration may lead to an increase in peripherally circulating FOXP3-positive regulatory immune cells, potentially hindering treatment options for patients with metastatic renal cell carcinoma. The study, published in Clinical Cancer Research, aimed to investigate the impact of IL-2-based therapy on the accumulation of FOXP3-positive immune cells in the tumor microenvironment.

Key Takeaways:

  • The administration of IL-2 may increase the frequency of peripherally circulating FOXP3-positive regulatory immune cells, which could compromise the treatment option for patients with metastatic renal cell carcinoma.
  • Baseline and on-treatment tumor core biopsies from 58 and 42 patients, respectively, showed a significant increase in absolute intratumoral FOXP3-positive immune cells comparing baseline and on-treatment biopsies (median 23 cells/mm² at baseline vs. median 89 cells/mm² at on-treatment).
  • Patients with high numbers of on-treatment FOXP3-positive cells (n = 31) had a 5-year survival rate of 19% (hazard ratio, 2.2; confidence interval, 1.03-4.5; P = 0.043).
  • The study concluded that intratumoral FOXP3-positive regulatory immune cells significantly increased during IL-2-based immunotherapy, and high numbers of on-treatment FOXP3-positive cells were correlated with poor prognosis in patients with metastatic renal cell carcinoma.
  • All long-term survivors (n = 5) were characterized by low-baseline FOXP3-positive cells and a modest absolute rise in FOXP3-positive cells.

Statistics:

  • 58 patients underwent baseline tumor core biopsies.
  • 42 patients underwent on-treatment tumor core biopsies.
  • The median intratumoral FOXP3-positive immune cells at baseline was 23 cells/mm² (range, 0-183).
  • The median intratumoral FOXP3-positive immune cells at on-treatment was 89 cells/mm² (range, 11-388).
  • 31 patients had high numbers of on-treatment FOXP3-positive cells.
  • The 5-year survival rate for patients with high numbers of on-treatment FOXP3-positive cells was 19% (hazard ratio, 2.2; confidence interval, 1.03-4.5; P = 0.043).

Sources:

  • Jensen, H. K., et al. "Increased Intratumoral FOXP3-positive Regulatory Immune Cells during Interleukin-2 Treatment in Metastatic Renal Cell Carcinoma." Clinical Cancer Research, vol. 15, no. 3, 2009, pp. 1052-1058.
  • American Association Cancer Research. Clinical Cancer Research.