In this book we provide insights into liver – cancer and immunology. Experts in the field provide an overview over fundamental immunological questions in liver cancer and tumorimmunology, which form the base for immune based approaches in HCC, which gain increasing interest in the community due to first promising results obtained in early clinical trials. Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death in the United States. Treatment options are limited. Viral hepatitis is one of the major risk factors for HCC, which represents a typical “inflammation-induced” cancer. Immune-based treatment approaches have revolutionized oncology in recent years. Various treatment strategies have received FDA approval including dendritic cell vaccination, for prostate cancer as well as immune checkpoint inhibition targeting the CTLA4 or the PD1/PDL1 axis in melanoma, lung, and kidney cancer. Additionally, cell based therapies (adoptive T cell therapy, CAR T cells and TCR transduced T cells) have demonstrated significant efficacy in patients with B cell malignancies and melanoma. Immune checkpoint inhibitors in particular have generated enormous excitement across the entire field of oncology, providing a significant benefit to a minority of patients.

Primary liver cancer (PLC), including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), and other rare tumors, is the third leading cause of cancer-related mortality. Of all primary liver cancer, HCC is the most common type. Evidence has accumulated that the tumor microenvironment (TME) plays a key role in fostering or restraining tumor development. The tumor microenvironment (TME), which includes molecular, cellular, extracellular matrix(ECM), and vascular signaling pathways, is a complex ecosystem. The interaction between the tumor microenvironment and cancer cells can enhance the malignant properties of tumors, including proliferation, angiogenesis, metastasis, and therapy resistance. In addition, the tumor microenvironment can also lead to abnormal angiogenesis and promote immunosuppression. HCC has been resistant to targeted therapy and immunotherapy. Therefore, further study of the tumor microenvironment of HCC may be helpful for the development of therapeutic methods for HCC.

A common feature of cancer metabolism is the ability to obtain essential nutrients from a nutrient-poor environment and use them to maintain viability as well as generate new biomass. Alterations in intracellular and extracellular metabolites can be accompanied by tumor-associated metabolic reprogramming with profound effects on gene expression, cell differentiation, and tumor microenvironment. In these cases, the metabolic microenvironment of the tumor itself can present an immunosuppressive environment that needs to be overcome. Specifically, it will help maximize the efficacy of cancer therapies by identifying targets that suppress or alter cancer metabolism to improve the tumor microenvironment nutrient availability or that modulate immune metabolism to bolster inflammation.

This volume evaluates the clinical patterns of resistance to sorafenib, the impact of trial design in the second-line setting and the current gold standard to define radiological resistance; describes the molecular mechanisms responsible for treatment resistance in HCC patients, including components of the immune system and tumor microenvironment; determines the role of the cancer stem cell phenotype in resistance; reviews the experimental models to study resistance; and addresses new approaches to overcome resistance to sorafenib, using successful examples from other malignancies.

This volume evaluates the clinical patterns of resistance to sorafenib, the impact of trial design in the second-line setting and the current gold standard to define radiological resistance; describes the molecular mechanisms responsible for treatment resistance in HCC patients, including components of the immune system and tumor microenvironment; determines the role of the cancer stem cell phenotype in resistance; reviews the experimental models to study resistance; and addresses new approaches to overcome resistance to sorafenib, using successful examples from other malignancies.

This book provides a comprehensive overview of the current limitations and unmet needs in Hepatocellular Carcinoma (HCC) diagnosis, treatment, and prevention. It also provides newly emerging concepts, approaches, and technologies to address challenges. Topics covered include changing landscape of HCC etiologies in association with health disparities, framework of clinical management algorithm, new and experimental modalities of HCC diagnosis and prognostication, multidisciplinary treatment options including rapidly evolving molecular targeted therapies and immune therapies, multi-omics molecular characterization, and clinically relevant experimental models. The book is intended to assist collaboration between the diverse disciplines and facilitate forward and reverse translation between basic and clinical research by providing a comprehensive overview of relevant areas, covering epidemiological trend and population-level patient management strategies, new diagnostic and prognostic tools, recent advances in the standard care and novel therapeutic approaches, and new concepts in pathogenesis and experimental approaches and tools, by experts and opinion leaders in their respective fields. By thoroughly and concisely covering whole aspects of HCC care, Hepatocellular Carcinoma serves as a valuable reference for multidisciplinary readers, and promotes the development of personalized precision care strategies that lead to substantial improvement of disease burden and patient prognosis in HCC.