The combined molecular adjuvant CASAC enhances the CD8+ T cell response to a tumor-associated self-antigen in aged, immunosenescent mice.

Background: Ineffective induction of T cell mediated immunity in older individuals remains a persistent challenge for vaccine development. Thus, there is a need for more efficient and sophisticated adjuvants that will complement novel vaccine strategies for the elderly. To this end, we have investigated a previously optimized, combined molecular adjuvant, CASAC (Combined Adjuvant for Synergistic Activation of Cellular immunity), incorporating two complementary Toll-like receptor agonists, CpG and polyI:C, a class-II epitope, and interferon (IFN)-γ in aged mice.

Glyco-engineered anti-EGFR mAb elicits ADCC by NK cells from colorectal cancer patients irrespective of chemotherapy.

Background: The epidermal growth factor receptor (EGFR) is overexpressed in colorectal cancer (CRC), and is correlated with poor prognosis, making it an attractive target for monoclonal antibody (mAb) therapy. A component of the therapeutic efficacy of IgG1 mAbs is their stimulation of antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells bearing the CD16 receptor. As NK cells are functionally impaired in cancer patients and may be further compromised upon chemotherapy, it is crucial to assess whether immunotherapeutic strategies aimed at further enhancing ADCC are viable.

The bone marrow functionally contributes to liver fibrosis.

Background & Aims: Bone marrow (BM) cells may transdifferentiate into or fuse with organ parenchymal cells. BM therapy shows promise in murine models of cirrhosis, and clinical trials of bone marrow stem cell therapy for organ healing are underway. However, the BM may contribute to scar-forming myofibroblasts in various organs including the liver.

Hepatic stem cells: from inside and outside the liver?

The liver is normally proliferatively quiescent, but hepatocyte loss through partial hepatectomy, uncomplicated by virus infection or inflammation, invokes a rapid regenerative response from all cell types in the liver to perfectly restore liver mass. Moreover, hepatocyte transplants in animals have shown that a certain proportion of hepatocytes in foetal and adult liver can clonally expand, suggesting that hepatoblasts/hepatocytes are themselves the functional stem cells of the liver. More severe liver injury can activate a potential stem cell compartment located within the intrahepatic biliary tree, giving rise to cords of bipotential transit amplifying cells (oval cells), that can ultimately differentiate into hepatocytes and biliary epithelial cells.

CD152 ligation by CD80 on T cells is required for the induction of unresponsiveness by costimulation-deficient antigen presentation.

Two apparently contradictory observations have been made concerning peripheral T cell tolerance; costimulation-deficient Ag presentation leads to unresponsiveness, and CTLA4 (CD152) ligation is required for unresponsiveness to be induced. This issue was addressed using a CD80- CD86low B cell line to present Ag to DO.11.