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Hepatobiliary Cancers and Immunology

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Abstract

Hepatocellular carcinoma (HCC) is the major leading cause of cancer-related death worldwide and mostly occurs in people with chronic liver disease or cirrhosis due to HBV and HCV infection, alcohol addiction, and nonalcoholic steatohepatitis. HCC cells evade or suppress the anti-tumor immune system by altering their characteristics and producing immunosuppressive molecules including cytokines/chemokines in concert with stromal cells in their tumor microenvironment (TME). In the HCC TME, tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs) play immunosuppressive and tumor-promoting roles, whereas cytotoxic T cells (CTLs) and natural killer (NK) cells, central players of the immune control of HCC, are functionally impaired. Several molecular targeted agents and immune checkpoint inhibitors are currently available for the treatment of advanced HCC, and their combination therapy could be a more potent new therapeutic. Alternative immunotherapeutic strategies including vaccine, immune cell-based therapy, or elimination of immunosuppressive cells are still actively under investigation toward HCC.

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Abbreviations

APCs:

antigen-presenting cells

BCLC:

Barcelona Clinic Liver Cancer

Breg:

regulatory B cells

CAFs:

cancer-associated fibroblasts

CAR:

chimeric antigen receptor

CCRK:

cell cycle-related kinase

CIK:

cytokine-induced killer

COX:

cyclooxygenase

CTLA:

cytotoxic T lymphocyte antigen

CTLs:

cytotoxic T cells

DCs:

dendritic cells

ENTPD2:

ectonucleoside triphosphate diphosphohydrolase 2

FDA:

Food and Drug Administration

GITR:

glucocorticoid-induced tumor necrosis factor receptor

GP73:

Golgi protein 73

GWAS:

genome-wide association study

HCC:

hepatocellular carcinoma

ICGC:

International Cancer Genome Consortium

IDO1:

indoleamine-2,3-dioxygenase 1

IFN:

interferon

IL:

interleukin

ILCs:

innate lymphoid cells

LAG:

lymphocyte-activation gene

MAGE:

melanoma-associated antigen

MDSCs:

myeloid-derived suppressor cells

MHC:

major histocompatibility complex

MICA:

major histocompatibility complex class I chain-related protein A

MICB:

major histocompatibility complex class I chain-related protein B

M-MDSCs:

monocytic MDSCs

NAFLD:

nonalcoholic fatty liver disease

NK:

natural killer

NO:

nitric oxide

NOX1:

NADPH oxidase 1

NSCLC:

non-small-cell lung carcinoma

PD-1:

programmed cell death 1

PGE2:

prostaglandin E2

PMN-MDSCs:

polymorphonuclear MDSCs

ROS:

reactive oxygen species

RTK:

receptor tyrosine kinase

SCF:

stem cell factor

SCNA:

somatic copy number alterations

TAA:

tumor-associated antigens

TACE:

transarterial chemoembolization

TAMs:

tumor-associated macrophages

TCGA:

The Cancer Genome Atlas

TCR:

T-cell receptor

TGF:

transforming growth factor

TIBs:

tumor-infiltrating B cells

TIGIT:

T-cell immunoreceptor with Ig and ITIM domains

TIM:

T-cell immunoglobulin and mucin-domain containing

TNF:

tumor necrosis factor

Treg:

regulatory T cells

ULBP:

UL16-binding proteins

VEGF-A:

vascular endothelial growth factor A

WHO:

World Health Organization

α-GalCer:

α-galactosylceramide

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

    Takahiro Kodama & Tetsuo Takehara

Authors
  1. Takahiro Kodama
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  2. Tetsuo Takehara
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Correspondence to Tetsuo Takehara .

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Editors and Affiliations

  1. Division of Rheumatology, Allergy and Clinical Immunology, The University of California School of Medicine, Davis, CA, USA

    M. Eric Gershwin

  2. Departments of Medicine and Surgery, Baylor College of Medicine, Houston, TX, USA

    John M. Vierling

  3. Department of Medicine, Teikyo University School of Medicine, Itabashi, Tokyo, Japan

    Atsushi Tanaka

  4. President, Hannover Medical School, Hannover, Germany

    Michael P. Manns

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Kodama, T., Takehara, T. (2020). Hepatobiliary Cancers and Immunology. In: Gershwin, M.E., M. Vierling, J., Tanaka, A., P. Manns, M. (eds) Liver Immunology . Springer, Cham. https://doi.org/10.1007/978-3-030-51709-0_31

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