Human CD96 Correlates to Natural Killer Cell Exhaustion and Predicts the Prognosis of Human Hepatocellular Carcinoma

• DOI: 10.1002/hep.30347
• Publication Date: 2018-11-09T07:04:21Z
• Authors: Haoyu Sun; Qiang Huang; Mei Huang; Hao Wen; Renyong Lin; Meijuan Zheng; Kun Qu; Kun Li; Haiming Wei; Weihua Xiao; Rui Sun; Zhigang Tian; Cheng Sun
• Keywords: TIGIT

Immune checkpoint blockade has become a promising therapeutic approach to reverse immune cell exhaustion. Coinhibitory CD96 and T‐cell immunoglobulin ITIM domain (TIGIT), together with costimulatory CD226, bind common ligand CD155. The balancing between three receptors fine‐tunes responses against tumors. In this study, we investigated the expression of CD96, TIGIT, CD226 in 55 fresh human hepatocellular carcinoma (HCC) samples, 236 paraffin‐embedded HCC 20 normal livers. cumulative percentage, absolute count, mean fluorescence intensity (MFI) + NK cells are significantly increased intratumoral tissues break balance receptors. Human functionally exhausted impaired interferon‐gamma (IFN‐γ) tumor necrosis factor‐alpha (TNF‐α) production, high gene interleukin (IL)‐10 transforming growth factor‐beta 1 (TGF‐β1), low T‐bet, IL‐15, perforin, granzyme B. addition, blocking CD96‐CD155 interaction specifically increases lysis HepG2 by cells. patients level or CD155 within strongly associated deteriorating disease condition shorter disease‐free survival (DFS) overall times. Patients higher percentage also exhibit DFS. High plasma TGF‐β1 up‐regulates dynamically shifts Blocking restores reverses dysfunction Conclusion: These findings indicate that poorer clinical outcomes. immunity tumors reversing exhaustion, suggesting possible role fighting liver cancer.