IgG Immune Complexes Inhibit Naïve T Cell Proliferation and Suppress Effector Function in Cytotoxic T Cells.

Elevated levels of circulating immune complexes are associated with autoimmunity and with worse prognoses in cancer. Here, we examined the effects of well-defined, soluble immune complexes (ICs) on human peripheral T cells. We demonstrate that IgG-ICs inhibit the proliferation and differentiation of a subset of naïve T cells but stimulate the division of another naïve-like T cell subset. Phenotypic analysis by multi-parameter flow cytometry and RNA-Seq were used to characterize the inhibited and stimulated T cells revealing that the inhibited subset presented immature features resembling those of recent thymic emigrants and non-activated naïve T cells, whereas the stimulated subset exhibited transcriptional features indicative of a more differentiated, early memory progenitor with a naïve-like phenotype. Furthermore, we show that while IgG1-ICs do not profoundly inhibit the proliferation of memory T cells, IgG1-ICs suppress the production of granzyme-ß and perforin in cytotoxic memory T cells. Our findings reveal how ICs can link humoral immunity and T cell function.

Management of Intrahepatic Cholangiocarcinoma.

Cholangiocarcinoma is a tumor that arises as a result of differentiation of the cholangiocytes and can develop from anywhere in the biliary tree. Subtypes of cholangiocarcinoma are differentiated based on their location in the biliary tree. If diagnosed early these can be resected, but most cases of intrahepatic cholangiocarcinoma present late in the disease course where surgical resection is not an option. In these patients who are poor candidates for resection, a combination of chemotherapy, locoregional therapies like ablation, transarterial chemo and radioembolization, and in very advanced and metastatic disease, external radiation are the available options. These modalities can improve overall disease-free and progression-free survival chances. In this review, we will discuss the risk factors and clinical presentation of intrahepatic cholangiocarcinoma, diagnosis, available therapeutic options, and future directions for management options.