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Immunotherapy of hepatocellular carcinoma: Unique challenges and clinical opportunities.

Pardee AD, Butterfield LH - Oncoimmunology (2012)

Bottom Line: Current therapies for advanced hepatocellular carcinoma (HCC) are marginally effective and exacerbate underlying liver disease.The ability of immunotherapy to elicit nontoxic, systemic, long-lived anti-tumor activity makes it particularly well-suited for use in the setting of HCC.Therapeutic regimens that both counteract these immunosuppressive mechanisms and amplify tumor-specific immunity are expected to profoundly improve clinical outcomes for HCC patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine; University of Pittsburgh School of Medicine; Pittsburgh, PA USA.

ABSTRACT
Current therapies for advanced hepatocellular carcinoma (HCC) are marginally effective and exacerbate underlying liver disease. The ability of immunotherapy to elicit nontoxic, systemic, long-lived anti-tumor activity makes it particularly well-suited for use in the setting of HCC. While therapeutic benefit has been achieved in early clinical trials, the efficacy of immune-based therapies is limited by several unique properties of HCC, most notably the inherently tolerogenic character of the liver in both healthy and diseased (chronically-infected or tumor-bearing) states. Therapeutic regimens that both counteract these immunosuppressive mechanisms and amplify tumor-specific immunity are expected to profoundly improve clinical outcomes for HCC patients.

No MeSH data available.


Related in: MedlinePlus

Figure 1. Evolving liver immunobiology during HCC development. Numerous tolerogenic factors, many of which are listed here, support immunoregulation in both the steady-state and diseased (chronically-infected or tumor-bearing) liver. These immunosuppressive mechanisms likely accumulate during HBV/HCV-mediated hepatocarcinogenesis and coexist in patients with advanced HCC lesions. See text for all associated references.
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Figure 1: Figure 1. Evolving liver immunobiology during HCC development. Numerous tolerogenic factors, many of which are listed here, support immunoregulation in both the steady-state and diseased (chronically-infected or tumor-bearing) liver. These immunosuppressive mechanisms likely accumulate during HBV/HCV-mediated hepatocarcinogenesis and coexist in patients with advanced HCC lesions. See text for all associated references.

Mentions: In summary, the liver is comprised of a dynamic network of specialized cell subsets that maintain immune privilege through redundant regulatory mechanisms. Three distinct liver microenvironments, varying with disease state and all polarized toward negative immune regulation, have been characterized (Fig. 1). These numerous tolerogenic factors may accumulate during HBV/HCV-mediated hepatocarcinogenesis and coincide in advanced HCC lesions, facilitating an aggressive and effective counterattack to anti-HCC immunity. Future studies will be needed to address this notion.


Immunotherapy of hepatocellular carcinoma: Unique challenges and clinical opportunities.

Pardee AD, Butterfield LH - Oncoimmunology (2012)

Figure 1. Evolving liver immunobiology during HCC development. Numerous tolerogenic factors, many of which are listed here, support immunoregulation in both the steady-state and diseased (chronically-infected or tumor-bearing) liver. These immunosuppressive mechanisms likely accumulate during HBV/HCV-mediated hepatocarcinogenesis and coexist in patients with advanced HCC lesions. See text for all associated references.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376967&req=5

Figure 1: Figure 1. Evolving liver immunobiology during HCC development. Numerous tolerogenic factors, many of which are listed here, support immunoregulation in both the steady-state and diseased (chronically-infected or tumor-bearing) liver. These immunosuppressive mechanisms likely accumulate during HBV/HCV-mediated hepatocarcinogenesis and coexist in patients with advanced HCC lesions. See text for all associated references.
Mentions: In summary, the liver is comprised of a dynamic network of specialized cell subsets that maintain immune privilege through redundant regulatory mechanisms. Three distinct liver microenvironments, varying with disease state and all polarized toward negative immune regulation, have been characterized (Fig. 1). These numerous tolerogenic factors may accumulate during HBV/HCV-mediated hepatocarcinogenesis and coincide in advanced HCC lesions, facilitating an aggressive and effective counterattack to anti-HCC immunity. Future studies will be needed to address this notion.

Bottom Line: Current therapies for advanced hepatocellular carcinoma (HCC) are marginally effective and exacerbate underlying liver disease.The ability of immunotherapy to elicit nontoxic, systemic, long-lived anti-tumor activity makes it particularly well-suited for use in the setting of HCC.Therapeutic regimens that both counteract these immunosuppressive mechanisms and amplify tumor-specific immunity are expected to profoundly improve clinical outcomes for HCC patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine; University of Pittsburgh School of Medicine; Pittsburgh, PA USA.

ABSTRACT
Current therapies for advanced hepatocellular carcinoma (HCC) are marginally effective and exacerbate underlying liver disease. The ability of immunotherapy to elicit nontoxic, systemic, long-lived anti-tumor activity makes it particularly well-suited for use in the setting of HCC. While therapeutic benefit has been achieved in early clinical trials, the efficacy of immune-based therapies is limited by several unique properties of HCC, most notably the inherently tolerogenic character of the liver in both healthy and diseased (chronically-infected or tumor-bearing) states. Therapeutic regimens that both counteract these immunosuppressive mechanisms and amplify tumor-specific immunity are expected to profoundly improve clinical outcomes for HCC patients.

No MeSH data available.


Related in: MedlinePlus