Journal Article

Distinct tumour antigen-specific T-cell immune response profiles at different hepatocellular carcinoma stages

He, Ning, Li, Kang, Zang, Chaoran, Sheng, Shoupeng, Qin, Ling, Zhao, Yanan, Peng, Yanchun, Li, Xi, Liu, Guihai, Sun, Jianping, Zhang, Honghai, Dong, Tao, Wang, Qi, Zhang, Yonghong, Zhao, Peng, Zhao, Yan

2021

Overview

Background 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. Methods 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. Results 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. Conclusions 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Ablation / Adolescent / Adult / Aged / Antigens / Antigens, Neoplasm - immunology / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cancer therapies / Cancer-testis antigen / Carcinoma, Hepatocellular - immunology / Carcinoma, Hepatocellular - pathology / Carcinoma, Hepatocellular - therapy / Case-Control Studies / CD4 antigen / CD8-Positive T-Lymphocytes - immunology / Cell culture / Cell surface antigens / Chemoembolization, Therapeutic - methods / Cirrhosis / Cytokines / Development and progression / Developmental stages / Distinction / Enzyme-linked immunosorbent assay / Female / Follow-Up Studies / Genetic aspects / Health aspects / Health Promotion and Disease Prevention / Hepatitis B / Hepatocellular carcinoma / Hepatoma / Humans / Immune response / Immune response (cell-mediated) / Immune system / Immunotherapy / Liver cancer / Liver cirrhosis / Liver Neoplasms - immunology / Liver Neoplasms - pathology / Liver Neoplasms - therapy / Lymphocytes / Lymphocytes T / Male / Medicine/Public Health / Middle Aged / Oncology / Patients / Peptides / Phenotypes / Prognosis / Radiofrequency ablation / Statistical analysis / Stem cells / Surgical Oncology / T cell immune response / T cells / Tumor antigens / Tumor necrosis factor-TNF / Tumors / Tumour-associated antigen / Young Adult / γ-Interferon