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Erschienen in: Cancer Immunology, Immunotherapy 6/2003

01.06.2003 | Original Article

High levels of Fas ligand and MHC class II in the absence of CD80 or CD86 expression and a decreased CD4+ T cell Infiltration, enables murine skin tumours to progress

verfasst von: Scott N. Byrne, Gary M. Halliday

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 6/2003

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Abstract

It is still not clear why some tumours will be recognized and destroyed by the immune system, and others will persist, grow, and eventually kill the host. It has been hypothesized that tumour cells might evade immunological destruction by expressing Fas ligand (FasL), a molecule which induces apoptosis in Fas+ target cells. However, the role of FasL in creating an immune privileged status within a tumour remains controversial. To determine whether FasL is associated with skin tumour progression, we developed a tumour model enabling us to compare two squamous cell carcinomas (SCC). One is a regressor SCC which spontaneously regresses after injection into syngeneic mice. The other is a progressor SCC which evades immunological destruction. Detailed flow cytometric analysis was used to study tumour cell expression of FasL, Fas, CD80, CD86 and MHC class II. We also analysed the percentage of apoptotic tumour cells in vivo using annexin V and correlated skin tumour progression with CD4 and CD8 T cell infiltration. Progressor tumours expressed high levels of FasL in vivo, which was virtually absent from regressor tumours. The percentage of progressor tumours expressing MHC II was significantly greater than regressor tumours, while neither tumour expressed CD80 or CD86 costimulatory molecules. Consistent with a regressor phenotype, the percentage of viable tumour cells was significantly lower for regressor compared to progressor tumours which coincided with a significantly larger CD4+ T cell infiltrate into the tumour mass. The results suggest that progression of skin tumours occurs if tumour cells express high levels of MHC II but not costimulatory molecules such as CD80 or CD86. This implies that tumours may induce anergy in CD4+ T cells via MHC II antigen presentation in the absence of costimulation. To ensure escape from the immune system, tumours may then kill these T cells via a FasL-dependent mechanism.
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Metadaten
Titel
High levels of Fas ligand and MHC class II in the absence of CD80 or CD86 expression and a decreased CD4+ T cell Infiltration, enables murine skin tumours to progress
verfasst von
Scott N. Byrne
Gary M. Halliday
Publikationsdatum
01.06.2003
Verlag
Springer-Verlag
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 6/2003
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-003-0380-0

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