Cancer-testis antigens and immunosurveillance in human cutaneous squamous cell and basal cell carcinomas.
OBJECTIVE
Nonmelanoma skin cancer is the most common cancer and comprises basal cell carcinoma (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 (CT) antigens and MHC class I (MHC-I) and the infiltration by immune cells in BCC and SCC.


METHODS
We determined the expression of 23 different CT-antigens in 63 BCC and 40 SCC biopsies of immunocompetent and in 20 biopsies of immunosuppressed SCC patients by reverse transcription-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 CT-antigen in 81% of BCC and in 40% of SCC. We did not detect CT-antigen-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, because 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.
Walter
Anne
A
Laboratory of Tumor Immunology, Department of Oncology, University Hospital Zurich, Zurich, Switzerland. Anne.Walter@usz.ch
Barysch
Marjam J
MJ
Behnke
Silvia
S
Dziunycz
Piotr
P
Schmid
Bruno
B
Ritter
Erika
E
Gnjatic
Sacha
S
Kristiansen
Glen
G
Moch
Holger
H
Knuth
Alexander
A
Dummer
Reinhard
R
van den Broek
Maries
M
D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002280:Basal Cell Carcinoma / Q000276:immunology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D015166:Monitoring, Immunologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D015395:Histocompatibility Antigens Class I