Cancer-Testis Antigens and Immunosurveillance in Human Cutaneous Squamous Cell and Basal Cell Carcinomas

Abstract

Purpose: 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.Experimental Design: 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 imiquimodtreated 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.

Spontaneous Peripheral T-cell Responses toward the Tumor-Associated Antigen Cyclin D1 in Patients with Clear Cell Renal Cell Carcinoma

“…Most tumors expressed more than one TAA, which has been described for other tumor entities (16)(17)(18), and which enables therapeutic-targeting of multiple antigens at the same time.…”

Hedgehog Pathway Inhibitors Promote Adaptive Immune Responses in Basal Cell Carcinoma

“…Although these are limited in number, our data suggest that these changes in the immune environment may be crucial for tumor control and highlight the poorly understood interface between targeted therapy and immune responses. BCCs frequently express multiple cancer testis antigens, but are also associated with relative absence of MHC class I molecules from tumor cells, and it has been hypothesized that BCCs produce immunosuppressive factors such as IL10 (2,21) and therefore are resistant to adaptive immune response. This might explain the absence of infiltrating CD8 þ cells in BCC.…”

“…Despite the presence of cancer testis and other tumor antigens, BCCs escape from immune surveillance by the downregulation of HLA class I expression (2). Recently, targeted therapy based on knowledge of BCC pathogenesis has become available either commercially or in the context of human clinical trials.…”

Aldara activates TLR7-independent immune defence

“…Recently, it was shown that Aldara treatment resulted in pDC-mediated tumour killing in a murine melanoma model 7 . We and others previously showed that treatment with IMQ and Aldara resulted in upregulation of MHC class I on tumour cells, recruitment of T cells into the tumour, enhancement of their effector function and mobilization of Langerhans cells and inflammatory DCs, as well as in interleukin (IL)-17 production by dermal gd-T cells 8,[9][10][11][12] .…”