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Differential expression of programmed cell death ligand 1 (PD-L1) and inflammatory cells in basal cell carcinoma
Matias Gompertz-Mattar1, Juan Perales1, Aditi Sahu2
1Department of Dermatology, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Diagonal Paraguay 362, 6th Floor, 8330077, Santiago, Chile.
Insights
This study found higher programmed cell death ligand (PD-L1) expression and T-lymphocyte infiltrates in Basal Cell Carcinoma (BCC) compared to normal skin. Nodular BCC showed the highest PD-L1, suggesting a potential therapeutic target.
Area of Science:
- Oncology
- Dermatology
- Immunology
Background:
- Basal Cell Carcinoma (BCC) is the most common skin cancer.
- Limited research exists on programmed cell death ligand (PD-L1) expression and immune infiltrates in BCC subtypes.
- Understanding the tumor microenvironment is crucial for developing targeted therapies.
Purpose of the Study:
- To evaluate PD-L1 expression and immune cell markers (CD4, CD8, FOXP3) in nodular, superficial, and morpheaform BCC.
- To compare these markers between BCC subtypes and normal sun-exposed skin.
- To identify potential therapeutic targets within BCC subtypes.
Main Methods:
- Retrospective study of 115 BCC samples (nodular, superficial, morpheaform) and 41 normal skin controls.
- Tissue microarrays (TMA) were used for Hematoxylin and Eosin (H&E) staining and immunohistochemistry (IHC) for PD-L1, CD4, CD8, and FOXP3.
- Non-automated quantification of intratumoral and stromal immune infiltrates.
Main Results:
- BCC samples exhibited significantly higher PD-L1, CD8, and FOXP3 expression compared to normal skin.
- Nodular BCC showed higher PD-L1 expression than other BCC subtypes.
- Low-risk BCC subtypes (superficial, nodular) had greater PD-L1 expression in immune infiltrates than high-risk subtypes.
Conclusions:
- Significant differences in PD-L1 expression and lymphocytic infiltrates exist among BCC subtypes and normal skin.
- Nodular BCC demonstrates the highest PD-L1 expression, indicating a potential target for therapy.
- Further research is needed to evaluate immune cell function in BCC.
Abstract:
Few studies have evaluated programmed cell death ligand (PD-L1) expression and lymphocytic infiltrates in Basal Cell Carcinoma (BCC). The objectives of this study are to assess PD-L1 expression and markers of local immune response in nodular, superficial, and morpheaform BCC, and compare it to normal, sun-exposed skin from the periphery of intradermal nevi. This was a retrospective study that included three histological subtypes of BCCs, and sun-exposed skin from the periphery of dermal nevi as quality controls. Tissue microarrays (TMA) were constructed with subsequent staining of H&E and immunohistochemistry (IHC) for CD4, CD8, FOXP3 and PD-L1. Non-automated quantification of the infiltrate in the intratumoral and stromal compartments on TMAs was performed. A total of 115 BCC (39 nodular, 39 morpheaform, and 37 superficial) and 41 sun-exposed skin samples were included (mean age 65.4 years; 52.6% females). BCC showed higher expression of PD-L1 (5.4 vs 0.7%, p < 0.001), CD8 (29.8 vs 19.7%, p = 0.002), and FOXP3 (0.3 vs 0.06%, p = 0.022) compared to sun-exposed skin. There was a higher PD-L1 expression in nodular BCC compared with other subtypes. Low-risk BCC subtypes (superficial and nodular) exhibited more PD-L1 expression in intratumoral and stromal immune infiltrates as compared to high-risk BCC subtypes. As a limitation, no immune cells function was evaluated in this study, only the presence/absence of T-lymphocyte sub-populations was recorded. Substantial differences in both PD-L1 expression and lymphocytic infiltrates were found amongst the histological subtypes of BCC and sun-exposed skin. Highest PD-L1 expression was found in nodular BCCs which suggests a potentially targetable strategy in the treatment of this most common BCC subtype.
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