Biomedical Information Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
Interventional Therapy Center of Liver Disease, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
BMC Cancer. 2021 Sep 8;21(1):1007. doi: 10.1186/s12885-021-08720-9.
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.
癌-睾丸抗原（CTAs）和肿瘤相关抗原（TAAs）在肝细胞癌（HCC）中频繁表达；然而，肿瘤抗原特异性 T 细胞免疫在 HCC 进展中的作用仍不清楚。我们在不同 HCC 阶段对 CTA 和 TAA 特异性 T 细胞反应进行了特征描述，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。采用 IFN-γ ELISPOT 检测 CTAs（包括 MAGE-A1、MAGE-A3、NY-ESO-1 和 SSX2）和两个 TAA（SALL4 和 AFP）的特异性 T 细胞反应，以对入组个体的 T 细胞免疫反应进行特征描述。采用短期 T 细胞培养分析 T 细胞的功能表型和反应性 T 细胞群体。
针对 CTAs 和 TAAs 的 T 细胞反应是 HCC 特异性的。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。经肝动脉化疗栓塞联合射频消融治疗后 1 年无复发生存提示 CTA 特异性反应具有保护作用。随着 HCC 的进展，四种 CTA 和 SALL4 特异性 T 细胞反应下降，而 AFP 特异性 T 细胞反应增加。与 AFP 特异性 T 细胞反应相比，观察到更高比例的 CD4+T 细胞特异性针对 CTA/SALL4。
IFN-γ ELISPOT 检测法对 HCC 患者的肿瘤抗原特异性 T 细胞反应特征进行了描述。在早期阶段，CTA 和 SALL4 特异性 T 细胞反应可能对控制 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特征。在 HCC 发展的早期阶段应考虑应用免疫疗法。
