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Depicting the Immunological Landscape of Basal Cell Carcinoma Subtypes
Isabella Dommann1, Gaetana Restivo1, Isabel Kolm2
1Department of Dermatology, University Hospital Zurich and Faculty of Medicine, University of Zurich, Zurich, Switzerland.
Background:
Anti-PD-1 response has been associated with higher PD-1 ligand (PD-L1) expression levels in different cancer types. Cemiplimab, an anti-PD-1 antibody, has been shown to induce a response rate of 31% and 22% in patients with locally advanced basal cell carcinoma (BCC) and metastatic BCC respectively, who have progressed or are intolerant to Hedgehog Inhibitors (HHi). The lower-than-expected efficacy of anti-PD-1 antibodies and limited and conflicting data on PD-L1 expression in BCC have prompted us to characterize the prerequisites for immune response-PD-L1, dendritic cells (DCs), and HLA expression with immunohistochemistry in different BCC morphological subtypes, namely superficial, nodular, sclerosing/infiltrative, and basosquamous.
Methods:
In this retrospective study, a total of 77 tumor samples from 4 BCC subtypes were analyzed by immunohistochemistry. Among the BCC subtypes, we assessed PD-L1 and CD11c + DCs expression within tumor and stroma, and HLA Class I expression in the tumor compared to the epidermis. Non-automated quantification of positive tumor cells and peri- and intratumoral immune cells was performed by a board-certified pathologist.
Results:
In all BCC subtypes, tumor cells (SOX9 positive) were negative for PD-L1. PD-L1 was expressed on intra- and peritumoral immune cells, predominantly in basosquamous BCCs, where 80% of the samples showed PD-L1 positivity in immune cells. DCs were predominantly found in the peritumoral area, mostly in basosquamous BCC, whereas superficial BCCs showed the least DCs. HLA class I expression was downregulated compared to epidermis in most specimens without significant differences among the subtypes.
Conclusion:
Our findings support previous reports on the immune-privileged status of BCC. Contrary to the literature, we could not confirm PD-L1 expression on BCC cells, but rather on the intra- and peritumoral immune cells. Given these results and the literature suggesting a tendency of higher immunoreactivity compared to other BCC subtypes, basosquamous BCC might be a better target for anti-PD-1 therapy as opposed to other subtypes.
