NKG2A is a NK cell exhaustion checkpoint for HCV persistence.

Exhaustion of cytotoxic effector natural killer (NK) and CD8 T cells have important functions in the establishment of persistent viral infections, but how exhaustion is induced during chronic hepatitis C virus (HCV) infection remains poorly defined. Here we show, using the humanized C/O mice permissive for persistent HCV infection, that NK and CD8 T cells become sequentially exhausted shortly after their transient hepatic infiltration and activation in acute HCV infection. HCV infection upregulates Qa-1 expression in hepatocytes, which ligates NKG2A to induce NK cell exhaustion.

GFI1 downregulation promotes inflammation-linked metastasis of colorectal cancer.

Inflammation is frequently associated with initiation, progression, and metastasis of colorectal cancer (CRC). Here, we unveil a CRC-specific metastatic programme that is triggered via the transcriptional repressor, GFI1. Using data from a large cohort of clinical samples including inflammatory bowel disease and CRC, and a cellular model of CRC progression mediated by cross-talk between the cancer cell and the inflammatory microenvironment, we identified GFI1 as a gating regulator responsible for a constitutively activated signalling circuit that renders CRC cells competent for metastatic spread.

Structural immunology of costimualtory and coinhibitory molecules.

The T cell costimulatory pathways are central to regulating immune responses, and targeting these pathways represents one of the most promising approaches for achieving immunotherapy. The molecular structures of costimulation revealed invaluable mechanistic insights underlying costimulatory receptor/ligand specificity, affinity, oligomeric state, and valency, which provided the bases for better manipulation of these signaling pathways. The incredible growth of this field led to identification of new members and unexpected interactions, revealing a complicated regulatory network of immune responses.

[Expression and significance of B7-H1 and its receptor PD-1 in human gastric carcinoma].

Objective: The B7-H1/PD-1 co-signaling pathway has recently been found to play a pivotal role in the immune evasion of tumor cells from host immune system. The aim of this study was to examine the B7-H1 and PD-1 expression and TILs status in gastric cancer and to elucidate the clinical relevance of B7-H1 and PD-1 to the pathogenesis of gastric carcinoma.

Methods: Immunohistochemistry and ANAE histochemical staining were used to investigate the in situ expression of B7-H1 and PD-1 and TILs status in the gastric tissues.

Expression of functional B7-H2 and B7.2 costimulatory molecules and their prognostic implications in de novo acute myeloid leukemia.

Purpose: The B7 family molecules have been shown to regulate immune responses in both positive and negative fashions. Their roles in the progression of human cancers, however, are not well established. The aim of this study was to examine whether leukemic cells of acute myeloid leukemia express functional B7 family molecules and, if so, whether such expression has any clinical significance.

B7-H4, a molecule of the B7 family, negatively regulates T cell immunity.

We identify a B7 family molecule, B7-H4, by protein sequence analysis and comparative molecular modeling. While B7-H4 mRNA is widely distributed in mouse and human peripheral tissues, cell surface expression of B7-H4 protein is limited and shows an inducible pattern on hematopoietic cells. Putative receptor of B7-H4 can be upregulated on activated T cells.