No 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.

The development of cancer immunotherapy and targeted therapy has reached an important inflection point in the history of melanoma. Immune checkpoint inhibitors and kinase inhibitors are today’s standard of care treatments in advanced melanoma patients. Treatment-related toxicities can be very intriguing and quite challenging. Sarcoidosis is a multisystemic granulomatous disease characterized by an aberrant immune response to unknown antigens, whereas sarcoid-like reactions (SLRs) refer to localized clinical features. We carried out a single-center observational study in patients with stage IIB–IV melanoma treated with BRAF/MEK inhibitors and immune checkpoint inhibitors. A description of the sarcoidosis-related manifestations was provided from patients’ records. We observated eight cases of SLRs in a cohort of 200 patients. The clinical courses were characterized by a variety of symptoms, accompanied by cutaneous signs and extracutaneous manifestations such as bilateral, hilar lymphadenopathy. We identified a histologically granulomatous inflammation involving the skin, the lungs, and the lymph nodes. Two patients presented with cutaneous lesions only, and three patients had lung involvement only. Three patients achieved complete and partial response of the melanoma disease, and three patients had stable disease. Disease progression was documented in two patients. The reported immune-related adverse events were mild to severe and in most of the cases were continued without any treatment cessation. SLRs appear during treatment with both kinase and immune checkpoint inhibitors. Awareness of these can avoid misdiagnosis of disease progression and unnecessary treatment changes.