Profile of Tumor Antigen-Specific CD8 T Cells in Patients With Hepatitis B Virus-Related Hepatocellular Carcinoma

Gehring, Adam J.; Ho, Zi Zong; Tan, Anthony T.; Aung, Myat Oo; Lee, Kang Hoe; Kc, Tan; Lim, Seng Gee; Bertoletti, Antonio

doi:10.1053/j.gastro.2009.04.045

Cited by 149 publications

(136 citation statements)

References 44 publications

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“…Exhausted T cells show decreased production of cytokines and cell proliferation, while being more likely to undergo apoptosis [26]. Exhaustion of T cells has been observed in HCC patients [27]. Fas and IFN-γ expression in CD8 + T cells is abnormal in HCC, suggesting defective cytotoxic function.…”

Section: Rationally Combining Anti-vegf Therapy With Checkpoint Inhibmentioning

confidence: 99%

Rationally Combining Anti-VEGF Therapy with Checkpoint Inhibitors in Hepatocellular Carcinoma

2016

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Hepatocellular carcinoma (HCC) is a fatal disease with rising incidence in the world. For advanced HCC, sorafenib, a multikinase inhibitor, is the only systemic therapy with proven survival benefits. Sorafenib is a pan-VEGF receptor inhibitor, and thus many studies have focused its antivascular effects. But VEGF also acts as an immunosuppressive molecule. VEGF can inhibit maturation of dendritic cells, promote immune suppressive cell infiltration and enhance immune checkpoint molecules expression. On the other hand, potent VEGF inhibition may increase tumor hypoxia, which could hinder antitumor immunity or immunotherapy. Thus, achieving synergy when combining anti-VEGF therapy with immunotherapy may require proper polarization of the tumor microenvironment by dose titration or combination with other immunomodulating agents.

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Section: Rationally Combining Anti-vegf Therapy With Checkpoint Inhibmentioning

confidence: 99%

Rationally Combining Anti-VEGF Therapy with Checkpoint Inhibitors in Hepatocellular Carcinoma

2016

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“…121 Apoptosis induction by NK cells might be one of the reasons HCC-specific CD8 1 T cells are reduced in HBV-related HCC. 122 Further studies are needed to delve into the opposing roles of NK cells in CHB to substantively exploit the potential of NK cells to treat chronic HBV infection and HCC. In addition, how NK cells quantitatively evaluate the strength of activating and inhibitory signals is unknown, as is the mechanism by which NK cells set their own activation threshold or become self-tolerant during tumor evasion.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

et al. 2014

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Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. There is a significant correlation between chronic hepatitis B virus (HBV) infection and hepatocarcinogenesis. As the first line of host defense against viral infections and tumors, natural killer (NK) cells express a large number of immune recognition receptors (NK receptors (NKRs)) to recognize ligands on hepatocytes, liver sinusoidal endothelial cells, stellate cells and Kupffer cells, which maintain the balance between immune response and immune tolerance of NK cells. Unfortunately, the percentage and absolute number of liver NK cells decrease significantly during the development and progression of HCC. The abnormal expression of NK cell receptors and dysfunction of liver NK cells contribute to the progression of chronic HBV infection and HCC and are significantly associated with poor prognosis for liver cancer. In this review, we focus on the role of NK cell receptors in anti-tumor immune responses in HCC, particularly HBV-related HCC. We discuss specifically how tumor cells evade attack from NK cells and how emerging understanding of NKRs may aid the development of novel treatments for HCC. Novel mono-and combination therapeutic strategies that target the NK cell receptor-ligand system may potentially lead to successful and effective immunotherapy in HCC. Keywords: activating receptor; hepatocellular carcinoma; inhibitory receptor; natural killer cell; natural killer receptor INTRODUCTION Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. 1 Common clinical risk factors for HCC include hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, heavy alcohol intake, steatohepatitis and diabetes. 2 Approximately 50% of HCC cases worldwide can be attributed to chronic HBV infection (CHB) and almost 75% of HCC cases occur in developing countries where HBV is endemic. 3,4 According to statistics, older male patients who are infected with HBV genotype C or co-infected with HCV, have high levels of viral load and have been exposed to the aflatoxin, or older male patients who have a family history of HCC tend to have a high risk of developing HCC. [5][6][7] Accumulating clinical and epidemiological evidence shows a significant correlation between chronic HBV infection and hepatocarcinogenesis. However, the underlying mechanisms

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“…Although the responses of tumor-specific cytotoxic T-lymphocyte had been reported in HCC patients, tumor regression is rarely observed (Gehring et al, 2009). Two major mechanisms are suggested to be responsible for the compromised tumor-specific killing: the dysfunction of cytolytic machineries and the increase of the inhibitory elements (Wu et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Associations Between Infiltrating Lymphocyte Subsets and Hepatocellular Carcinoma

Guo

Yang²,

Yang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Profile of Tumor Antigen-Specific CD8 T Cells in Patients With Hepatitis B Virus-Related Hepatocellular Carcinoma

Cited by 149 publications

References 44 publications

Rationally Combining Anti-VEGF Therapy with Checkpoint Inhibitors in Hepatocellular Carcinoma

Rationally Combining Anti-VEGF Therapy with Checkpoint Inhibitors in Hepatocellular Carcinoma

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

Associations Between Infiltrating Lymphocyte Subsets and Hepatocellular Carcinoma

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