HLA expression as a risk factor for metastases of cutaneous squamous-cell carcinoma in organ- transplant recipients

Estella de Jong*, Koen D. Quint, Abdoelwaheb El Ghalbzouri, Robert M. Verdijk, Jelle J. Goeman, Sebastiaan Heidt, Frans H.J. Claas, Johan W. de Fijter, Roel E. Genders, Maarten H. Vermeer, Jan Nico Bouwes Bavinck

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Solid organ-transplant recipients (SOTR) have an increased risk of cutaneous squamous-cell carcinoma (cSCC), metastasis and death from cSCC. In immunocompetent patients with mucosal SCC, downregulation of HLA class I is associated with poor prognosis. Since the degree of HLA expression on tumor cells could play a role in immunogenicity and pathophysiology of cSCC metastasis, we hypothesized that decreased HLA expression is associated with an increased risk of metastasis. 


We compared HLA expression between primary metastasized cSCCs, their metastases, and non-metastasized cSCCs from the same patients. Samples were stained for HLA-A, HLA-B/-C and quantified by calculating the difference in immunoreactivity score (IRS) of the primary cSCC compared with all non-metastasized cSCCs. 


The mean IRS score for HLA-B/C expression was 2.07 point higher in metastasized compared to non-metastasized cSCCs (p = 0.065, 95 % CI −0.18–4.32). 83.3 % of the primary metastasized cSCCs had an IRS score of 4 or higher, compared to 42.9 % in non-metastasized cSCCs. Moderately to poorly differentiated cSCCs had more HLA class I expression compared to well-differentiated cSCCs. 


Contrary to immunocompetent patients, HLA-B/C expression tends to be upregulated in metastasized cSCC compared to non-metastasized cSCC in SOTR, suggesting that different tumor escape mechanisms play a role in SOTR compared to immunocompetent patients.

Original languageEnglish
Pages (from-to)208-213
Number of pages6
JournalHuman Immunology
Issue number3
Early online date6 Jan 2023
Publication statusPublished - Mar 2023

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