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Immune responses in patients with metastatic renal cell carcinoma treated with dendritic cells pulsed with tumor

A Soleimani1, A Berntsen, I M Svane

  • 1Department of International Health, Immunology and Microbiology, The Panum Institute, University of Copenhagen, Denmark.

Scandinavian Journal of Immunology
|October 31, 2009
PubMed

Insights

Dendritic cell (DC) vaccination in metastatic renal cell carcinoma (mRCC) patients showed a TH1 immune response in those with stable disease. Immune marker levels increased during vaccination but did not differentiate between stable and progressive disease outcomes.

Area of Science:

  • Immunology
  • Oncology
  • Vaccine Development

Background:

  • Metastatic renal cell carcinoma (mRCC) patients have poor prognosis.
  • A subset of mRCC patients benefit from immunotherapy, including dendritic cell (DC) vaccination.
  • Understanding immune responses to DC vaccination is crucial for improving outcomes.

Purpose of the Study:

  • To analyze immune responses, including T-cell proliferation and TH1/TH2 balance, in mRCC patients receiving DC vaccination.
  • To identify potential systemic immune response biomarkers correlating with clinical outcomes.
  • To evaluate immune responses in both HLA-A2 negative and positive mRCC patients.

Main Methods:

  • Phase I/II trial involving mRCC patients vaccinated with autologous DCs pulsed with tumor lysate or peptides.
  • Analysis of peripheral blood mononuclear cell (PBMC) proliferation and T-helper 1 (TH1)/T-helper 2 (TH2) balance.
  • Measurement of serum cytokine levels (IL-10, IL-12, IL-15, IL-17, IL-18) during vaccination.

Main Results:

  • A spontaneous TH1 predominance of tumor lysate-specific T cells was observed in HLA-A2 negative mRCC patients who achieved stable disease (SD) before vaccination.
  • Patients with progressive disease (PD) showed a mixed TH1/TH2 response.
  • The TH1/TH2 balance remained unchanged during vaccination, despite increased T-cell responses.
  • Serum levels of IL-12, IL-17, and IL-18 increased during vaccination, but without significant differences between SD and PD groups.
  • IL-10 and IL-15 were not detectable in serum.

Conclusions:

  • Pre-existing TH1 immune bias may be associated with stable disease in mRCC patients undergoing DC vaccination.
  • While vaccination elicits systemic immune responses, specific cytokine changes did not clearly distinguish between clinical responders and non-responders.
  • Further research is needed to identify reliable biomarkers for predicting response to DC immunotherapy in mRCC.

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