Abstract
Background
Traditional systemic treatments for unresectable, recurrent, and/or advanced sebaceous carcinoma (SC) are ineffective. Tumoral immune microenvironment characterization is essential for considering immune checkpoint inhibitors as a treatment option.
Methods
A total of 173 resected SCs were reviewed. Clinical information, lesion size, and location were collected. Microscopic examination documented histopathologic features and expression of immunohistochemical markers PD-L1 and CD8. PD-L1 percentage was assessed amongst tumor (PD-L1 + Tu) and immune infiltrating cells (PD-L1 + Inf). Each case was attributed a combined positive score (CPS) following Head and Neck squamous cell carcinoma recommendations. PD-L1 expression was evaluated according to clinicopathologic parameters. Human Papilloma Virus presence (HPV) was analyzed using PCR microarray scanning.
Results
A therapeutically relevant CPS was seen in 51.4% of cases. Higher PD-L1 + Tu, PD-L1 + Inf, and CPSs were positively associated with greater lesion size and an extraocular location. No association was seen with patient age or gender. 9.2% of SCs showed PD-L1 + Tu ≥ 1, while 52.0% showed PD-L1 + Inf ≥ 1. A higher CD8 + T-lymphocyte density was significantly associated with a higher CPS, PD-L1 + Tu, and PD-L1 + Inf. Tumor-associated T-cell infiltrate’s density was higher along tumor periphery. HPV-16, HPV-43, HPV-52, and HPV-66 were detected in 8.4% of SCs. There was no significant association between HPV status, PD-L1 expression, and CPS. A significant number of SCs express PD-L1 at therapeutic levels. Nevertheless, PD-L1 expression shows a higher intertumoral heterogeneity, in extraocular than in biologically distinct periocular cases.
Conclusion
Our data support the need for large-scale prospective studies evaluating anti-PD-L1 immunotherapy mainly in extraocular SC treatment.
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Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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This study was funded by the American University of Beirut.
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M.Sa. participated in concept and design, statistical analysis, data interpretation and drafting of the manuscript. M.Sh, S.B., and U.N.S. participated in the acquisition and interpretation of data. R.E.H and F.I.A participated in administrative, technical, and material support. R.M participated in concept design in addition to technical support and data analysis. A.L. participated in concept design and the acquisition of data I.K. oversaw concept development and the critical revision of the manuscript for important intellectual content.
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Saliba, M., Shaheen, M., Hajj, R.E. et al. PD-L1 expression in sebaceous carcinomas. Cancer Immunol Immunother 70, 1907–1915 (2021). https://doi.org/10.1007/s00262-020-02821-3
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DOI: https://doi.org/10.1007/s00262-020-02821-3