Abstract
PURPOSE: Non melanoma skin cancer (NMSC) is the most common cancer and comprises basal cell (BCC) and squamous cell carcinoma (SCC). The incidence of SCC increases drastically in immunosuppressed individuals, suggesting a critical role of the immune system in controlling SCC. To find an explanation for the selective immunosurveillance of SCC, we investigated the expression of cancer-testis antigens (CTA), MHC class I and the infiltration by immune cells in BCC and SCC. Experimental design: We determined the expression of 23 different CTA in 63 BCC and 40 SCC biopsies of immunocompetent and in 20 biopsies of immunosuppressed SCC patients by RT-PCR and immunohistochemistry. IgG responses to 36 tumor antigens were measured by Western Blotting and ELISA. MHC-I expression and CD8+ T cell infiltration were analyzed by immunohistochemistry in BCC and SCC of immunocompetent and immunosuppressed patients and in imiquimod-treated BCC patients.RESULTS: We found expression of at least one CTA in 81% of BCC and in 40% of SCC. We did not detect CTA-specific serum IgG. Most SCC, but not BCC, expressed MHC-I and were infiltrated with CD8+ cells. Imiquimod-treated BCC expressed MHC-I and were infiltrated by CD8+ T cells.CONCLUSIONS: We propose that immunosurveillance controls SCC, but not BCC, as the latter lacks MHC-I. This fits with the increased incidence of SCC in immunosuppressed individuals and may explain the relatively low prevalence of CT-antigen expression in SCC as a result of CD8+ T cell driven immunoediting.