Details

Autor(en) / Beteiligte

• Lim, Chun Jye
• Lee, Yun Hua
• Pan, Lu
• Lai, Liyun
• Chua, Camillus
• Wasser, Martin
• Lim, Tony Kiat Hon
• Yeong, Joe
• Toh, Han Chong
• Lee, Ser Yee
• Chan, Chung Yip
• Goh, Brian Kp
• Chung, Alexander
• Heikenwälder, Mathias
• Ng, Irene Ol
• Chow, Pierce
• Albani, Salvatore
• Chew, Valerie

Titel

Multidimensional analyses reveal distinct immune microenvironment in hepatitis B virus-related hepatocellular carcinoma

Ist Teil von

• Gut, 2019-05, Vol.68 (5), p.916-927

Ort / Verlag

England: BMJ Publishing Group LTD

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• Chronic inflammation induced by chronic hepatitis B virus (HBV) infection increases the risk of hepatocellular carcinoma (HCC). However, little is known about the immune landscape of HBV-related HCC and its influence on the design of effective cancer immunotherapeutics. We interrogated the immune microenvironments of HBV-related HCC and non-viral-related HCC using immunohistochemistry and cytometry by time-of-flight (CyTOF). On identifying unique immune subsets enriched in HBV-related HCC, we further interrogated their phenotypes and functions using next-generation sequencing (NGS) and in vitro T-cell proliferation assays. In-depth interrogation of the immune landscapes showed that regulatory T cells (T ) and CD8 resident memory T cells (T ) were enriched in HBV-related HCC, whereas Tim-3 CD8 T cells and CD244 natural killer cells were enriched in non-viral-related HCC. NGS of isolated T and T from HBV-related HCC and non-viral-related HCC identified distinct functional signatures associated with T-cell receptor signalling, T-cell costimulation, antigen presentation and programmed cell death protein 1 (PD-1) signalling. T and T from HBV-related HCC expressed more PD-1 and were functionally more suppressive and exhausted than those from non-virus-related HCC. Furthermore, immunosuppression by PD-1 T could be reversed with anti-PD-1 blockade. Using multiplexed tissue immunofluorescence, we further demonstrated that T and T contributed to overall patient survival: T were associated with a poor prognosis and T were associated with a good prognosis in HCC. We have shown that the HBV-related HCC microenvironment is more immunosuppressive and exhausted than the non-viral-related HCC microenvironment. Such in-depth understanding has important implications in disease management and appropriate application of immunotherapeutics.