Related Experiment Videos
Soluble tumor necrosis factor receptor expression in patients with metastatic renal cell carcinoma treated with
A Belldegrun1, W Pierce, D Sayah
1Department of Surgery, UCLA School of Medicine 90024-1738.
Abstract:
Two distinct types of soluble tumor necrosis factor alpha receptors (sTNFRs), which are felt to represent proteolytic cleavage products of the extracellular domains of membrane-bound TNFRs of molecular mass, 55 and 75 kDa, are found in the serum and urine of humans. We have measured the serum concentrations of these receptors in eight patients with metastatic renal cell carcinoma during treatment with interleukin-2 (IL-2)-based immunotherapy. The mean pretreatment concentration of sTNFR-55 kDa (p < 0.05) but not sTNFR-75 kDa was significantly elevated prior to the onset of immunotherapy. In one patient the concentrations of both sTNFRs decreased dramatically following removal of the primary tumor. There were significant increases in the concentrations of both sTNFRs in patients treated with IL-2-based therapy that included in vivo primed tumor infiltrating lymphocytes (pTILs); some of these patients eventually achieved a complete response to therapy. These data demonstrate that sTNFR-55 kDa is elevated in patients with metastatic renal cell carcinoma prior to therapy and that IL-2-based therapy that included pTIL cells results in a further increase in sTNFRs.
Insights
Soluble tumor necrosis factor alpha receptors (sTNFRs) are elevated in metastatic renal cell carcinoma patients before treatment. Interleukin-2 (IL-2) immunotherapy with tumor infiltrating lymphocytes further increases sTNFR levels.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Soluble tumor necrosis factor alpha receptors (sTNFRs), specifically 55 kDa and 75 kDa, are cleavage products of membrane-bound receptors.
- These receptors are detectable in human serum and urine.
Purpose of the Study:
- To measure serum concentrations of sTNFR-55 kDa and sTNFR-75 kDa in patients with metastatic renal cell carcinoma (mRCC).
- To evaluate changes in sTNFR levels during interleukin-2 (IL-2)-based immunotherapy, particularly with tumor-infiltrating lymphocytes (pTILs).
Main Methods:
- Serum samples from eight mRCC patients were analyzed before and during IL-2 immunotherapy.
- Concentrations of sTNFR-55 kDa and sTNFR-75 kDa were quantified.
Main Results:
- Pretreatment sTNFR-55 kDa levels were significantly elevated in mRCC patients compared to baseline.
- IL-2-based therapy including pTILs led to significant increases in both sTNFR-55 kDa and sTNFR-75 kDa.
- One patient showed decreased sTNFR levels after primary tumor removal.
Conclusions:
- Elevated sTNFR-55 kDa is a potential biomarker in metastatic renal cell carcinoma prior to therapy.
- IL-2 immunotherapy combined with pTILs modulates sTNFR levels, indicating a biological response.
- Further research into sTNFRs as predictive or prognostic markers in mRCC immunotherapy is warranted.