CD8+ T Cell Responses during HCV Infection and HCC

Abstract

Chronic hepatitis C virus (cHCV) infection is a major global health burden and the leading cause of hepatocellular carcinoma (HCC) in the Western world. The course and outcome of HCV infection is centrally influenced by CD8⁺ T cell responses. Indeed, strong virus-specific CD8⁺ T cell responses are associated with spontaneous viral clearance while failure of these responses, e.g., caused by viral escape and T cell exhaustion, is associated with the development of chronic infection. Recently, heterogeneity within the exhausted HCV-specific CD8⁺ T cells has been observed with implications for immunotherapeutic approaches also for other diseases. In HCC, the presence of tumor-infiltrating and peripheral CD8⁺ T cell responses correlates with a favorable prognosis. Thus, tumor-associated and tumor-specific CD8⁺ T cells are considered suitable targets for immunotherapeutic strategies. Here, we review the current knowledge of CD8+ T cell responses in chronic HCV infection and HCC and their respective failure with the potential consequences for T cell-associated immunotherapeutic approaches.

Keywords: CD8+ T cells; HCC; HCV; T cell exhaustion; checkpoint blockade therapy.

Figure 1

Tumor antigens in the context of hepatocellular carcinoma (HCC). Tumor-specific antigens (neoantigens), tumor-associated antigens (TAA: overexpressed antigens, tumor testis antigens, and oncofetal antigens), and viral antigens are detectable in HCC patients.

Figure 2

Perspectives of CD8⁺ T cells in immunotherapeutic approaches. CD8⁺ T cells may have potential roles as targets and biomarkers in immunotherapy.