The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Multidimensional analyses reveal distinct immune microenvironment in hepatitis B virus-related hepatocellular carcinoma
Open accessAbstract
Background and aims: 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. Methods: 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. Results: In-depth interrogation of the immune landscapes showed that regulatory T cells (T REG) and CD8+ resident memory T cells (T RM) 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 REG and T RM 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 REG and T RM 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 REG could be reversed with anti-PD-1 blockade. Using multiplexed tissue immunofluorescence, we further demonstrated that T REG and T RM contributed to overall patient survival: T REG were associated with a poor prognosis and T RM were associated with a good prognosis in HCC. Conclusion: 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.
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Self-citationChallenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma
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Hepatocellular carcinoma: signaling pathways and therapeutic advances
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Metadata
- Authors
- Lim, C. J., Lee, Y. H., Pan, L., Lai, L., Chua, C., Wasser, M., Lim, T. K. H., Yeong, J., Toh, H. C., Lee, S. Y., Chan, C. Y., Goh, B. K., Chung, A., Heikenwälder, M., Ng, I. O., Chow, P., Albani, S., & Chew, V.
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2018-07-03
- Volume
- 68
- Issue
- 5
- Pages
- 916-927
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2810928105
- Cited by
- 357
- References
- 52
- FWCI
- 9.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Lim, C. J., Lee, Y. H., Pan, L., Lai, L., Chua, C., Wasser, M., Lim, T. K. H., Yeong, J., Toh, H. C., Lee, S. Y., Chan, C. Y., Goh, B. K., Chung, A., Heikenwälder, M., Ng, I. O., Chow, P., Albani, S., & Chew, V. (2019). Multidimensional analyses reveal distinct immune microenvironment in hepatitis B virus-related hepatocellular carcinoma. Gut. https://doi.org/10.1136/gutjnl-2018-316510
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