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In situ hybridisation for cytokine gene transcripts in the solid tumour microenvironment
D Vitolo1, A Kanbour, J T Johnson
1Pittsburgh Cancer Institute, Pennsylvania 15213.
European Journal of Cancer (Oxford, England : 1990)
|January 1, 1993
Summary
Tumours with immunogenic antigens activate many immune cells, while others suppress them. Transforming growth factor beta (TGF-beta) may down-regulate anti-tumour responses in head and neck cancers.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Mononuclear cells (MNC) infiltrate solid tumours.
- The expression of cytokine genes by these infiltrating MNC is not fully understood.
- Understanding MNC cytokine gene expression can reveal tumour immune evasion mechanisms.
Purpose of the Study:
- To investigate the expression of cytokine genes in MNC infiltrating human solid tumours.
- To correlate MNC cytokine gene expression with tumour type and antigenicity.
- To explore the role of specific cytokines, such as TGF-beta, in modulating anti-tumour responses.
Main Methods:
- In situ hybridisation using 35S-labelled cDNA antisense probes.
- Analysis of cytokine gene transcripts for IL2, IFN-gamma, TNF-alpha, IL1-beta, TGF-beta, and IL2R.
- Evaluation of fresh-frozen tissue samples from ovarian, breast, and head and neck squamous cell carcinomas (SCCHN).
Main Results:
- Ovarian and non-mucinous breast carcinomas showed rare positive MNC.
- Mucinous breast carcinomas and all SCCHN exhibited numerous MNC expressing cytokine genes (IL2, IFN-gamma, TNF-alpha, IL2R, TGF-beta).
- In SCCHN, MNC expressing cytokine genes were localized around tumour metastases in lymph nodes.
Conclusions:
- Tumours expressing immunogenic antigens (e.g., mucin) attract and activate numerous MNC.
- Tumours may suppress or fail to activate infiltrating MNC functions.
- TGF-beta produced by activated MNC in SCCHN may mediate local down-regulation of anti-tumour responses.