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Immunotherapy for hepatocellular carcinoma patients: is it ready for prime time?

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Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second most common cause of cancer death worldwide. Current treatment options for patients with intermediate and advanced HCC are limited, and there is an unmet need for novel therapeutic approaches. HCC is an attractive target for immunomodulation therapy, since it arises in an inflammatory milieu due to hepatitis B and C infections and cirrhosis. However, a major barrier to the development and success of immunotherapy in patients with HCC is the liver’s inherent immunosuppressive function. Recent advances in the field of cancer immunology allowed further characterization of immune cell subsets and function, and created new opportunities for therapeutic modulation of the immune system. In this review, we present the different immune cell subsets involved in potential immune modulation of HCC, discuss their function and clinical relevance, review the variety of immune therapeutic agents currently under investigation in clinical trials, and outline future research directions.

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Abbreviations

CIK:

Cytokine-induced killer

DFS:

Disease-free survival

GPC-3:

Glypican-3

HCC:

Hepatocellular carcinoma

KC:

Kupffer cells

LAG-3:

Lymphocyte activation gene 3

MDSC:

Myeloid-derived suppressor cells

NKT:

Natural killer T

OS:

Overall survival

PR:

Partial response

SD:

Stable disease

T-reg:

T-regulatory

TACE:

Transarterial chemoembolization

Tim-3:

T-cell immunoglobulin mucin 3

TME:

Tumor microenvironment

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Acknowledgements

Joseph Obeid and Craig Slingluff Jr. would like to thank the National Cancer Institute for the funding provided for salary support NCI T32 CA163177 and NCI P30 CA044579, respectively.

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Authors and Affiliations

  1. Department of Surgery, University of Virginia, Charlottesville, VA, USA

    Joseph M. Obeid, Victor M. Zaydfudim & Craig L. Slingluff Jr.

  2. Division of Hematology-Oncology, Department of Medicine, University of Virginia, Charlottesville, VA, USA

    Paul R. Kunk

  3. Department of Pathology, University of Virginia, Charlottesville, VA, USA

    Timothy N. Bullock

  4. Department of Medical Oncology, Dana-Farber Cancer Institute Harvard Medical School, 450 Brookline Avenue, M1B13, Boston, MA, 02215, USA

    Osama E. Rahma

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  1. Joseph M. Obeid
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Correspondence to Osama E. Rahma.

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Osama Rahma receives research support from Merck and is a speaker for activities supported by educational grants from Bristol-Meyers Squibb and Merck. Craig Slingluff Jr. received material from Merck for an ongoing clinical trial. All other authors have nothing to report.

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Obeid, J.M., Kunk, P.R., Zaydfudim, V.M. et al. Immunotherapy for hepatocellular carcinoma patients: is it ready for prime time?. Cancer Immunol Immunother 67, 161–174 (2018). https://doi.org/10.1007/s00262-017-2082-z

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