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ABSTRACT
Hepatobiliary and pancreatic cancers along with other gastrointestinal malignancies remain the leading cause of cancer-related deaths worldwide. Strategies developed in the recent years on immunotherapy and cancer vaccines in the setting of primary liver cancer as well as in pancreatic cancer are the scope of this review. Significance of orthotopic and autochthonous animal models which mimic and/or closely reflect human malignancies allowing for a prompt and trustworthy analysis of new therapeutics is underlined. Combinational approaches that on one hand, specifically target a defined cancer-driving pathway, and on the other hand, restore the functions of immune cells, which effector functions are often suppressed by a tumor milieu, are shown to have the strongest perspectives and future directions. Among combinational immunotherapeutic approaches a personalized- and individual cancer case-based therapy is of special importance.
Abbreviations
| ADC | = | Antibody-Drug Conjugate |
| AFP | = | α-Fetoprotein |
| ASPH | = | Aspartate-β-Hydroxylase |
| BTC | = | Biliary Tract Cancers |
| CAF | = | Carcinoma-Associated Fibroblast |
| CART | = | Chimeric Antigen Receptor-Modified T Cell |
| CCA | = | Cholangiocarcinoma |
| CEA | = | Cardioembryonic Antigen |
| CIK | = | Cytokine-Induced Killer Cells |
| Cmab | = | Cetuximab |
| CMV | = | Cytomegalovirus |
| CSF1R | = | Colony Stimulating Factor 1 Receptor |
| CTA | = | Cancer-Testis Antigens |
| CTL | = | Cytotoxic T Lymphocytes |
| CTLA-4 | = | Cytotoxic T-Lymphocyte-Associated Protein 4 |
| CXCR | = | C-X-C-Motif-Chemokine Receptor |
| DAC | = | 5-aza-20-deoxycytidine |
| DC | = | Dendritic Cells |
| DNA | = | Desoxyribonucleic Acid |
| DTH | = | Delayed-type Hypersensitivity |
| EGFR | = | Epidermal Growth Factor Receptor |
| ENO1 | = | Enolase 1 |
| EpCAM | = | Epithelial Cell Adhesion Molecule |
| ERBB2IP | = | Erbb2 Interacting Protein |
| FAK | = | Focal Adhesion Kinase |
| FAP | = | Fibroblast Activation Protein |
| FDA | = | Food and Drug Administration |
| FOXM1 | = | Forkhead Box M1 |
| GM-CSF | = | Granulocyte Macrophage Colony-Stimulating Factor |
| H-1PV | = | Human Papillomavirus |
| HBV | = | Hepatitis B Virus |
| HCC | = | Hepatocellular Carcinoma |
| HLA | = | Human Leukocyte Antigen |
| hMSH2 | = | Homo sapiens mutS Homolog 2 |
| HSCT | = | Haematopoietic Stem Cell Transplantation |
| hTERT | = | Human Telomerase Reverse Transcriptase |
| i.d. | = | Intradermal |
| i.v. | = | Intravenous |
| ICC | = | Intrahepatic Cholangiocarcinoma |
| IFN-γ | = | Interferon-γ |
| IGF | = | Insulin-Like Growth Factor |
| IGFIR-α | = | Insulin-Like Growth Factor I Receptor α |
| IL | = | Interleukin |
| IL-17RE | = | IL-17 Receptor E |
| iNKT | = | Invariant Natural Killer Cells |
| L1CAM | = | L1 Cell Adhesion Molecule |
| mAb | = | Monoclonal Antibody |
| MDC | = | Macrophage-Derived Chemokine |
| MDSC | = | Myeloid-Derived Suppressor Cells |
| MSC | = | Mesenchymal Stem Cells |
| MSPα | = | Macrophage-Stimulating Protein α |
| MUC1 | = | Mucin 1 |
| NASH | = | Non-Alcoholic Steatohepatitis |
| NK | = | Natural Killer Cells |
| NKT | = | Natural Killer T Cells |
| OS | = | Overall Survival |
| PAUF | = | Pancreatic Adenocarcinoma Up-Regulated Factor |
| PBL | = | Peripheral Blood Lymphocytes |
| PBMC | = | Peripheral Blood Mononuclear Cells |
| PD-1 | = | Programmed Cell Death 1 |
| PDAC | = | Pancreatic ductal adenocarcinoma |
| PD-L1 | = | Programmed Cell Death Ligand 1 |
| PFS | = | Progression-Free Survival |
| PGK2 | = | Phosphoglycerate Kinase 2 |
| PSC | = | Primary Sclerosing Cholangitis |
| PSCA | = | Prostate Stem Cell Antigen |
| rIL | = | Recombinant Interleukin |
| RNA | = | Ribonucleic acid |
| s.c. | = | Subcutaneous |
| SASP | = | Senescence-Associated Secretory Phenotype |
| SBRT | = | Stereotactic Body Radiation Therapy |
| SDF1α | = | Stromal Cell-Derived 1 α |
| SEREX | = | Serological Identification of Antigens by Recombinant Expression Cloning |
| TAA | = | Tumor-Associated Antigen |
| TACE | = | Transarterial Chemoembolization |
| TCR | = | T Cell Receptor |
| TGF-β | = | Transforming Growth Factor β |
| Th | = | T Helper Cell |
| TIL | = | Tumor-Infiltrating Lymphocyte |
| TLA | = | Tertiary Lymphoid Aggregates |
| Treg | = | Regulatory T Cells |
| WES | = | Whole Exome Sequencing |
| WHO | = | World Health Organization |
| WT1 | = | Wilm´s Tumor 1 |
| WTS | = | Whole Transcriptome Sequencing |
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Funding
This work was supported by the German Research Foundation, DFG (YE 151/2–1 to T.Y.), by the Fritz Thyssen Foundation (Ref.10.16.1031 MN to T.Y.), by the Young Academy Program of the Hannover Medical School (to T.Y.) and by the Wilhelm Sander Foundation (Nr. 2013.107.1 to T.Y. and M.M.)