Department of Dermatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands.
Department of Dermatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands.
Hum Immunol. 2023 Mar;84(3):208-213. doi: 10.1016/j.humimm.2022.12.002. Epub 2023 Jan 6.
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.
实体器官移植受者(SOTR)患皮肤鳞状细胞癌(cSCC)、cSCC 转移以及因 cSCC 死亡的风险增加。在黏膜 SCC 免疫功能正常的患者中,HLA Ⅰ类下调与预后不良相关。由于肿瘤细胞上 HLA 表达的程度可能在 cSCC 转移的免疫原性和病理生理学中发挥作用,我们假设 HLA 表达降低与转移风险增加相关。
我们比较了来自同一患者的原发性转移性 cSCC、转移灶和非转移性 cSCC 之间的 HLA 表达。通过计算原发性 cSCC 与所有非转移性 cSCC 之间免疫反应性评分(IRS)的差异来对 HLA-A、HLA-B/-C 进行染色并进行定量。
与非转移性 cSCC 相比,转移性 cSCC 的 HLA-B/C 表达 IRS 评分平均高 2.07 分(p=0.065,95%CI -0.18-4.32)。83.3%的原发性转移性 cSCC 的 IRS 评分为 4 或更高,而非转移性 cSCC 中为 42.9%。中-低分化 cSCC 的 HLA Ⅰ类表达高于高分化 cSCC。
与免疫功能正常的患者相反,在 SOTR 中,与非转移性 cSCC 相比,转移性 cSCC 中 HLA-B/C 表达趋于上调,这表明不同的肿瘤逃逸机制在 SOTR 中发挥作用,与免疫功能正常的患者不同。