| First Author | Zong L | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 221 |
| PubMed ID | 30644386 | Mgi Jnum | J:270552 |
| Mgi Id | MGI:6277435 | Doi | 10.1038/s41467-018-08096-8 |
| Citation | Zong L, et al. (2019) Breakdown of adaptive immunotolerance induces hepatocellular carcinoma in HBsAg-tg mice. Nat Commun 10(1):221 |
| abstractText | Hepatitis B virus (HBV) can induce chronic inflammation, cirrhosis, and eventually hepatocellular carcinoma (HCC). Despite evidence suggesting a link between adaptive immunity and HBV-related diseases in humans, the immunopathogenic mechanisms involved are seldom described. Here we show that expression of TIGIT, a promising immune checkpoint in tumor immunotherapy, increases with age on hepatic CD8(+) T cells in HBsAg-transgenic (HBs-tg) mice whose adaptive immune system is tolerant to HBsAg. TIGIT blockade or deficiency leads to chronic hepatitis and fibrosis, along with the emergence of functional HBsAg-specific cytotoxic T lymphocytes (CTLs), suggesting adaptive immune tolerance could be broken by TIGIT blockade or deficiency. Importantly, HBsAg vaccination further induces nonresolving inflammation and HCC in a CD8(+) T cell-dependent manner in TIGIT-blocked or -deficient HBs-tg mice. Therefore, CD8(+) T cells play an important role in adaptive immunity-mediated tumor progression and TIGIT is critical in maintenance of liver tolerance by keeping CTLs in homeostatic balance. |
