Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.
Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Cancer Sci. 2019 Jun;110(6):1842-1852. doi: 10.1111/cas.14022. Epub 2019 May 18.
Human lymphocyte antigen (HLA) class I molecules play a central role in cytotoxic T lymphocytes (CTL)-based antitumor immunity. However, the expression rate of HLA class I in cancer cells remains a topic of discussion. We compared HLA class I expression levels between cancer cells and surrounding non-tumorous hepatocytes in 20 early-stage hepatocellular carcinoma (HCC) patients by immunohistochemistry using EMR 8-5. The expression levels of HLA class I were classified as negative, incomplete positive or complete positive. Similarly, for various types of solid cancers, HLA class I expression was examined. For the HLA class I expression in cancer cells, among 20 HCC patients, 13 were complete positive, 3 were incomplete positive, and 4 were negative. In addition, 15 (75.0%) had higher expression levels of HLA class I in cancer cells compared with that in surrounding non-tumorous hepatocytes. An interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) assay indicated that cancer cells with positive expression of HLA class I had strong sensitivity to antigen-specific CTL. We suggested that HLA class I expression in cancer cells could be involved in the clinical prognosis of HCC patients. Similarly, 66.7%, 100.0%, 66.7% and 62.5% of patients with early-stage pancreatic, gallbladder, esophageal and breast cancers, respectively, had higher expression levels of HLA class I in cancer cells than in surrounding normal tissue cells. We suggest that in several early-stage solid cancers, including HCC, HLA class I expression levels in cancer cells are higher than that in surrounding normal tissue cells, which could result in the anti-tumor effect of CTL-based cancer immunotherapy.
人类淋巴细胞抗原 (HLA) Ⅰ类分子在细胞毒性 T 淋巴细胞 (CTL) 介导的抗肿瘤免疫中发挥核心作用。然而，癌细胞中 HLA Ⅰ类的表达率仍是一个讨论的话题。我们通过免疫组织化学方法使用 EMR8-5 比较了 20 例早期肝细胞癌 (HCC) 患者的癌细胞和周围非肿瘤性肝细胞中 HLA Ⅰ类的表达水平。HLA Ⅰ类的表达水平分为阴性、不完全阳性或完全阳性。同样，我们检查了各种类型的实体癌中的 HLA Ⅰ类表达。对于癌细胞中的 HLA Ⅰ类表达，在 20 例 HCC 患者中，13 例为完全阳性，3 例为不完全阳性，4 例为阴性。此外，与周围非肿瘤性肝细胞相比，15 例 (75.0%) 的癌细胞中 HLA Ⅰ类表达水平更高。干扰素-γ (IFN-γ) 酶联免疫斑点 (ELISPOT) 分析表明，HLA Ⅰ类阳性表达的癌细胞对抗原特异性 CTL 具有很强的敏感性。我们推测癌细胞中 HLA Ⅰ类的表达可能与 HCC 患者的临床预后有关。同样，在早期胰腺癌、胆囊癌、食管癌和乳腺癌患者中，分别有 66.7%、100.0%、66.7%和 62.5%的患者癌细胞中 HLA Ⅰ类的表达水平高于周围正常组织细胞。我们推测，在包括 HCC 在内的几种早期实体癌中，癌细胞中 HLA Ⅰ类的表达水平高于周围正常组织细胞，这可能导致 CTL 为基础的癌症免疫治疗的抗肿瘤作用。
