Download the ebooks for this Research Topic: Volume I.A: ¦PDF¦ ¦EPUB Volume I.B: ¦PDF¦ ¦ EPUB Hepatobiliary tumor, mainly including hepatocellular carcinoma, cholangiocarcinoma and gallbladder cancer, is a group of highly aggressive malignancies. Hepatocellular carcinoma, cholangiocarcinoma and gallbladder cancer have different biological characters, histopathological traits, and treatment strategies, but have similar clinical features such as silent early symptom and extremely poor prognosis. The diagnostic, predictive or prognostic tumor biomarkers of hepatobiliary cancers are in unmet need. In contrast to the poor outcome, the treatment options to hepatobiliary cancers are very limited. It is still controversial about the effects of chemotherapy and radiotherapy of hepatobiliary cancer. FDA-approved targeted drugs are only Sorafenib and Lenvatinib for hepatocellular carcinoma, and Pemigatinib for cholangiocarcinoma. Unfortunately, these drugs are only effective for 5%-30% patients. Therefore, more attention should be called upon on investigating effective biomarkers and drug targets, stratifying high-risk patients, guiding precise treatments, and developing therapeutic strategies for hepatobiliary cancers. This Research Topic aims at discussing the current knowledge and proceedings of diagnostic, predictive and prognostic tumor biomarkers in hepatobiliary cancer, and presenting the recent advances on new drug targets and potential targeted therapies of hepatobiliary cancer. We welcome submissions of Review, Mini-Review, Clinical Trial and Original Research articles covering, but not limited to, the following topics: 1. new diagnostic/prognostic factors, biomarkers and/or risk factors in hepatobiliary tumors 2. new drug targets, and oncogenic or tumor suppressive molecular mechanism of the novel targets 3. new intervention or targeted therapy in hepatobiliary tumors 4. new findings of bioinformatics or high-throughput methods such as mass spectrometry and genome-wide association studies or which may help screen the potential biomarkers of hepatobiliary tumors 5. clinical studies such as cohort study or RCT to identify new risks or treatment therapies in hepatobiliary tumors 6. basic, pharmacological, preclinical or clinical study of potential drugs targeting hepatobiliary tumors Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.

Intestinal flora is a diversified and dynamic micro-ecosystem, whose structure and function have become a research hotspot in life sciences and medicine. The close relationship between intestinal flora and metabolic diseases has been verified by numerous studies. Traditional Chinese medicine (TCM) is used for disease prevention and treatment within China and is attracting attention and receiving more and more recognition from other countries all over the world. Consequently, the interaction of the two hotspots deserves further investigation. Although TCM has been put into practice for thousands of years, the study of its specific mechanism of action and related targets for the treatment of endocrine diseases is still at an exploratory stage. For TCM with oral administration as the main usage, the key targets of their active ingredients may be inextricably linked to the decomposition and metabolic effects of certain intestinal bacterium. All these hypotheses need to be tested further.

The complex interactions between the innate and adaptive immune systems function to recognize and clear pathogens or transformed cells, but inefficient interactions between these two systems can result in harmful immunologic responses including chronic infections and the development of cancer. Several hallmarks of dysfunctional adaptive immune responses often detected in tumors share specific features with ineffective immunity in chronic infections. The members of the micromilieu actively participate in the process of tumorigenesis or chronification of infection by modulating innate and adaptive immune system interactions leading e.g. to insufficient T cell responses. The best example is given by the acquisition of an “exhausted” state of cytotoxic CD8+ T cells (CTLs) responding to chronic infections or tumors that are associated with elevated expression of inhibitory receptors and impaired cytokine response. Targeting these major inhibitory pathways by immune checkpoint blockers represents a prime example of successful clinical translation of tumor-specific immunotherapies. Understanding the mechanisms behind (mal)adaptations of the immune system is crucial for achieving therapeutic benefits. The establishment and co-evolution of a dynamic microenvironment niche constituted by the recruitment of numerous cell types dampen immune responses and thus contribute to the development of neoplastic transformation as well as infection. Although there are examples of successful immunotherapeutic approaches (CAR-T cells, immune checkpoint inhibitors, or mRNA vaccination), a large percentage of patients with cancer or chronic infections still do not benefit from these therapies or develop severe immune-related adverse events. The reasons for these failures are not well understood. A possible explanation might be that current immunotherapies target predominantly the effector arm of the immune system by trying to reactivate dysfunctional T cells, but do not sufficiently address the influence of the innate immune system and the contributions of the tumor microenvironment (TME) niche. The main problem we would like to address in this special issue is how inappropriate function of the innate immune system affects adaptive immunity and contributes to inefficient anti-cancer immunity and chronification of infections. The central goal is to provide a more precise understanding of the various (common and novel) immune evasion mechanisms in cancers and in chronic infections to obtain a detailed map of common and disease-specific immune escape checkpoints. To that aim, we want to compile a wide array of interdisciplinary studies exploring a comparative and multi-layered analysis of mechanisms responsible for inefficient immune responses, including novel approaches i.e. multi-omics or epigenetic signaling. We would also like to combine studies from different fields, including basic and clinical immunology, oncology, and virology/microbiology. We welcome the submission of Original Research, Review, Mini-Review, Methods, Case report, and Perspective articles that cover, but are not limited to the following topics: • Convergent mechanisms supporting immune escape in preclinical models (tumors and chronic infections) • Convergent evasion mechanisms mediated by tumor-infiltrating suppressive cells (Treg, MDSC, macro-phages, soluble mediators, signaling, metabolism, ...) • Convergent immune evasion mechanisms mediated by chronic infection (viral or parasite) • Novel strategies to modulate the TME by direct or indirect targeting of immune suppressor cells. • Approaches to enhance persistence and resilience of anticancer T cells • Combinatorial therapeutic strategies (mRNA, antibodies, immune checkpoint blockers …) that target convergent immune evasion mechanisms Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.

Topic Editor Dr. Kasper is co-founder of Symbiotix Biotherapeutics. The other Topic Editors declare no competing interests with regards to the Research Topic theme.