Combined hepatocellular cholangiocarcinoma: Controversies to be addressed

Combined hepatocellular cholangiocarcinoma(CHC) accounts for 0.4%-14.2% of primary liver cancer cases and possesses pathological features of both hepatocellular carcinoma and cholangiocarcinoma. Since this disease was first described and classified in 1949, the classification of CHC has continuously evolved. The latest definition and classification of CHC by the World Health Organization is based on the speculation that CHC arises from hepatic progenitor cells. However, there is no evidence demonstrating the common origin of different components of CHC. Furthermore, the definition of CHC subtypes is still ambiguous and the identification of CHC subtype when a single tumor contains many components has remained unresolved. In addition, there is no summary on the newly recognized histopathology features or the contribution of CHC components to prognosis and outcome of this disease. Here we provide a review of the current literature to address these questions.

Tolerogenic dendritic cells and their applications in transplantation

In transplantation immunology, the ultimate goal is always to successfully and specifically induce immune tolerance of allografts. Tolerogenic dendritic cells （toI-DCs） with immunoregulatory functions have attracted much attention as they play important roles in inducing and maintaining immune tolerance. Here, we focused on tol-DCs that have the potential to promote immune tolerance after solid-organ transplantation. We focus on their development and interactions with other regulatory cells, and we also explore various toI-DC engineering protocols. Harnessing tol-DCs represents a promising cellular therapy for promoting long-term graft functional survival in transplant recipients that will most likely be achieved in the future.

Roles of cell fusion, hybridization and polyploid cell formation in cancer metastasis

Cell-cell fusion is a normal biological process playing essential roles in organ formation and tissue differentiation,repair and regeneration.Through cell fusion somatic cells undergo rapid nuclear reprogramming and epigenetic modifications to form hybrid cells with new genetic and phenotypic properties at a rate exceeding that achievable by random mutations.Factors that stimulate cell fusion are inflammation and hypoxia.Fusion of cancer cells with non-neoplastic cells facilitates several malignancy-related cell phenotypes,e.g.,reprogramming of somatic cell into induced pluripotent stem cells and epithelial to mesenchymal transition.There is now considerable in vitro,in vivo and clinical evidence that fusion of cancer cells with motile leucocytes such as macrophages plays a major role in cancer metastasis.Of the many changes in cancer cells after hybridizing with leucocytes,it is notable that hybrids acquire resistance to chemo-and radiation therapy.One phenomenon that has been largely overlooked yet plays a role in these processes is polyploidization.Regardless of the mechanism of polyploid cell formation,it happens in response to genotoxic stresses and enhances a cancer cell’s ability to survive.Here we summarize the recent progress in research of cell fusion and with a focus on an important role for polyploid cells in cancer metastasis.In addition,we discuss the clinical evidence and the importance of cell fusion and polyploidization in solid tumors.

Inhibitory Receptors of the Immune System:Functions and Therapeutic Implications

The immune system has a remarkable ability to respond to seemingly endless antigens.In essence,a productive immune response takes place along a well defined but treacherous line,that is to effectively eradicate pathogens,and at the same time avoid causing damage to self organs.This type of response is fine-tuned,at least in part,by a complex array of pathways that either promote or inhibit the activation of innate and adaptive immune cells.Much effort has been focused on pathways that can support immune activation.In this article,we review specifically pathways that can inhibit immune responses and maintain immune homeostasis,highlighting our recent understanding on the role of inhibitory receptors that selectively engage the self MHC class I molecules and the B7 superfamily members,we also discuss the inhibitory Fc receptors and inhibitory cytokines and how such pathways,either individually or collectively,regulate innate and adaptive immune responses.Finally,we summarize new emerging approaches on how such negative pathways can be therapeutically modulated in various disease settings.