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Lack of interleukin-2 (IL-2) expression and selective expression of IL-10 mRNA in human renal cell carcinoma
1MTC, Karolinska Institute, Stockholm, Sweden.
Abstract:
Freshly isolated tumor-infiltrating lymphocytes (TIL) are often functionally deficient. Since one of the key functional parameters of an immune response is the local production of cytokines, we studied the expression of cytokine genes in freshly isolated renal cancer tissue. Using a PCR-assisted mRNA amplification assay, the constitutive expression of mRNA for 10 different cytokines was assessed in renal cancer tissue. We compared the cytokine mRNA expression in freshly isolated samples of renal carcinomas, renal cancer cell lines established from the tumor samples, peripheral blood mononuclear cells (PBMC) and non-tumor kidney tissue isolated from the same patients. IL-10 mRNA expression was detected only in tumor samples, while renal cancer lines, PBMC and non-tumorous kidney tissues were devoid of this cytokine. One-third of the tumor samples but none of the normal kidney samples also expressed G-CSF mRNA. IL-6, TNF-alpha and IFN-gamma mRNA were expressed non-selectively in tumors, PBMC and normal rental tissue. Expression of IL-2, IL-3 and IL-4 mRNA was not detected in any of the tissues analyzed. Established renal cancer lines exhibited expression of IL-1 alpha, IL-6, TNF-alpha and GM-CSF. Culture of tumor-derived T cells with anti-CD3 monoclonal antibody (MAb) resulted in expression of IL-2, IL-3 and IL-4 mRNA. In contrast, none of these cytokines was detected in culture with recombinant human IL-2 alone. Since IL-10 is known to suppress antigen presentation, these findings have important implications for the possible in vivo role of IL-10 as a suppressor of local anti-tumor response.
Insights
Tumor-infiltrating lymphocytes (TIL) in kidney cancer show altered cytokine gene expression. Interleukin-10 (IL-10) mRNA was found only in tumors, suggesting a role in suppressing anti-tumor immunity.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Freshly isolated tumor-infiltrating lymphocytes (TIL) often exhibit functional deficiencies.
- Cytokine production is a critical parameter of immune response efficacy.
Purpose of the Study:
- To investigate the constitutive expression of cytokine genes in freshly isolated renal cancer tissue.
- To compare cytokine mRNA expression between renal tumors, cancer cell lines, peripheral blood mononuclear cells (PBMC), and non-tumor kidney tissue.
Main Methods:
- Utilized a PCR-assisted mRNA amplification assay to assess cytokine gene expression.
- Analyzed mRNA for 10 different cytokines in various kidney tissue and cell samples.
Main Results:
- Interleukin-10 (IL-10) mRNA was exclusively detected in tumor samples, not in cell lines, PBMC, or normal kidney tissue.
- Granulocyte-colony stimulating factor (G-CSF) mRNA was found in one-third of tumors but not normal kidney tissue.
- Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-alpha), and Interferon-gamma (IFN-gamma) mRNA were expressed across tumors, PBMC, and normal tissue.
Conclusions:
- The exclusive presence of IL-10 mRNA in renal tumors suggests its potential role in suppressing local anti-tumor immune responses.
- Findings indicate that IL-10 may impair antigen presentation, impacting the effectiveness of the local immune surveillance against cancer.