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

BMC Cancer

Ling Qin¹  Kang Li¹  Jianping Sun¹  Chaoran Zang²  Qi Wang²  Yonghong Zhang²  Guihai Liu³  Yan Zhao⁴  Yanan Zhao⁵  Ning He⁶  Shoupeng Sheng⁶  Honghai Zhang⁶  Peng Zhao⁶  Xi Li⁷  Yanchun Peng⁷  Tao Dong⁷ 

[1] Biomedical Information Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China;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;Biomedical Information Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China;MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK;CAMS Oxford Institute, Nuffield Department of Medicine, Oxford University, Oxford, UK;Clinical Laboratory Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China;Department of Radiology and Research Institute of Radiology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China;Interventional Therapy Center of Liver Disease, Beijing YouAn Hospital, Capital Medical University, Beijing, China;MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK;CAMS Oxford Institute, Nuffield Department of Medicine, Oxford University, Oxford, UK;

关键词: Cancer-testis antigen;    Distinction;    Hepatocellular carcinoma;    T cell immune response;    Tumour-associated antigen;   

DOI  :  10.1186/s12885-021-08720-9

来源: Springer

【 摘 要 】

BackgroundCancer-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.MethodsFifty-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.ResultsT 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.ConclusionsThe 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.

【 授权许可】

CC BY