Pathology Department, Faculty of Medicine.
Liver Institute, Menoufia University, Shebein Elkom, Egypt.
Appl Immunohistochem Mol Morphol. 2021 Mar 1;29(3):188-200. doi: 10.1097/PAI.0000000000000865.
Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Tumor-infiltrating lymphocytes (TILs) are a class of cells that form the tumor microenvironment and thus have an effect on carcinogenesis. The aim of this study was to investigate the immunohistochemical expression of CD8, CD4, cytotoxic T lymphocyte-associated protein-4 (CTLA-4), and granzyme B in HCC and their correlation with clinicopathologic parameters and prognosis. This study was carried out on 112 cases of HCC. High percentage of CD8+ TILs was associated with large tumors and adjacent noncirrhotic liver. High percentage of CD4+ TILs and high CD4 to CD8 ratio were associated with nonviral etiology, low alpha fetoprotein, and direct acting antiviral treatment. High percentage of CTLA-4-positive TILs tended to be associated with high-grade HCC, while a high percentage of CTLA-4 in tumor cells was associated with multiple lesions and low tumor grade. High percentage of granzyme B+ TILs was associated with low grade, early stage, and absence of tumor recurrence. High CD4 percentage and high CD4/CD8 ratio affected patients' overall survival. There is a dynamic interaction between the different subsets of lymphocytes in the environment of HCC manifested by coparallel expression of CD4 and CD8 augmenting the expression of CTLA-4, and only CD8 augments the expression of granzyme B. This opens the gate for the beneficial role of immunotherapy in the management of HCC, reducing recurrence and improving survival.
肝细胞癌（HCC）是肝脏最常见的原发性恶性肿瘤。肿瘤浸润淋巴细胞（TILs）是一类形成肿瘤微环境的细胞，因此对癌变有影响。本研究旨在研究 HCC 中 CD8、CD4、细胞毒性 T 淋巴细胞相关蛋白 4（CTLA-4）和颗粒酶 B 的免疫组织化学表达及其与临床病理参数和预后的关系。本研究共纳入 112 例 HCC 患者。高比例的 CD8+TIL 与大肿瘤和相邻非肝硬化肝脏有关。高比例的 CD4+TIL 和高 CD4/CD8 比值与非病毒性病因、低甲胎蛋白和直接作用抗病毒治疗有关。高比例的 CTLA-4 阳性 TIL 倾向于与高级别 HCC 相关，而肿瘤细胞中高比例的 CTLA-4 与多发病灶和低肿瘤分级相关。高比例的颗粒酶 B+TIL 与低级别、早期和无肿瘤复发有关。高 CD4 百分比和高 CD4/CD8 比值影响患者的总生存期。HCC 环境中不同淋巴细胞亚群之间存在动态相互作用，表现为 CD4 和 CD8 的共平行表达增强 CTLA-4 的表达，而只有 CD8 增强颗粒酶 B 的表达。这为免疫疗法在 HCC 管理中的有益作用开辟了大门，减少了复发并提高了生存率。
