Cancer-testis antigens (CTAs) and tumour-associated antigens (TAAs) are frequently expressed in hepatocellular carcinoma (HCC); however, the role of tumour-antigen-specific T cell immunity in HCC progression is poorly defined. We characterized CTA- and TAA-specific T cell responses in different HCC stages and investigated their alterations during HCC progression. Fifty-eight HCC patients, 15 liver cirrhosis patients, 15 chronic hepatitis B patients and 10 heathy controls were enrolled in total. IFN-γ ELSPOT using CTAs, including MAGE-A1, MAGE-A3, NY-ESO-1, and SSX2, and two TAAs, SALL4 and AFP, was performed to characterize the T-cell immune response in the enrolled individuals. The functional phenotype of T cells and the responsive T cell populations were analyzed using short-term T-cell culture. T cell responses against CTAs and TAAs were specific to HCC. In early-stage HCC patients, the SALL4-specific response was the strongest, followed by MAGE-A3, NY-ESO-1, MAGE-A1 and SSX2. One-year recurrence-free survival after transcatheter arterial chemoembolization plus radiofrequency ablation treatment suggested the protective role of CTA-specific responses. The four CTA- and SALL4-specific T cell responses decreased with the progression of HCC, while the AFP-specific T cell response increased. A higher proportion of CD4+ T cells specific to CTA/SALL4 was observed than AFP-specific T cell responses. The IFN-γ ELISPOT assay characterized distinct profiles of tumour-antigen-specific T cell responses in HCC patients. CTA- and SALL4-specific T cell responses may be important for controlling HCC in the early stage, whereas AFP-specific T cell responses might be a signature of malignant tumour status in the advanced stage. The application of immunotherapy at an early stage of HCC development should be considered.

中文翻译：

---

不同肝细胞癌阶段的不同肿瘤抗原特异性 T 细胞免疫反应谱

癌睾丸抗原 (CTA) 和肿瘤相关抗原 (TAA) 经常在肝细胞癌 (HCC) 中表达；然而，肿瘤抗原特异性 T 细胞免疫在 HCC 进展中的作用尚不清楚。我们表征了不同 HCC 阶段的 CTA 和 TAA 特异性 T 细胞反应，并研究了它们在 HCC 进展过程中的变化。共纳入58例HCC患者、15例肝硬化患者、15例慢性乙型肝炎患者和10例健康对照者。使用 CTA（包括 MAGE-A1、MAGE-A3、NY-ESO-1 和 SSX2）以及两种 TAA（SALL4 和 AFP）进行 IFN-γ ELSPOT，以表征入组个体的 T 细胞免疫反应。使用短期 T 细胞培养分析 T 细胞的功能表型和反应性 T 细胞群。T 细胞针对 CTA 和 TAA 的反应是 HCC 特有的。在早期 HCC 患者中，SALL4 特异性反应最强，其次是 MAGE-A3、NY-ESO-1、MAGE-A1 和 SSX2。经导管动脉化疗栓塞加射频消融治疗后一年无复发生存表明 CTA 特异性反应的保护作用。随着 HCC 的进展，四种 CTA 和 SALL4 特异性 T 细胞反应减少，而 AFP 特异性 T 细胞反应增加。与 AFP 特异性 T 细胞反应相比，观察到 CTA/SALL4 特异性 CD4+ T 细胞比例更高。IFN-γ ELISPOT 测定表征了 HCC 患者肿瘤抗原特异性 T 细胞反应的不同特征。CTA 和 SALL4 特异性 T 细胞反应可能对于早期控制 HCC 很重要，而 AFP 特异性 T 细胞反应可能是晚期恶性肿瘤状态的标志。应考虑在 HCC 发展的早期阶段应用免疫治疗。