Danielle Corrigan

[Science] Dividing ectodermal cells disassembled ECM attachment formed by integrin-mediated focal adhesions next to mesodermal cells, allowing macrophages to move their nuclei ahead and invade between two immediately adjacent tissues.

[Science Immunology] Researchers reported that the LynB splice variant of the Src-family kinase Lyn exerted a dominant immunosuppressive function in vivo, whereas the LynA isoform was uniquely required to restrain autoimmunity in female mice.

[Science Immunology] Scientists used an in vitro differentiation system and human skin–grafted mice to study memory T cell generation from circulating human memory T cell subsets.

[Cell Metabolism] Glycolysis, including both lactate fermentation and pyruvate oxidation, orchestrates CD8+ T cell differentiation. However, how mitochondrial pyruvate metabolism and uptake controlled by the mitochondrial pyruvate carrier (MPC) impact T cell function and fate remains elusive. We found that genetic deletion of MPC drives CD8+ T cell differentiation toward a memory phenotype. Metabolic flexibility induced by MPC inhibition facilitated acetyl-coenzyme-A production by glutamine and fatty acid oxidation that results in enhanced histone acetylation and chromatin accessibility on pro-memory genes. However, in the tumor microenvironment, MPC is essential for sustaining lactate oxidation to support CD8+ T cell antitumor function. We further revealed that chimeric antigen receptor (CAR) T cell manufacturing with an MPC inhibitor imprinted a memory phenotype and demonstrated that infusing MPC inhibitor-conditioned CAR T cells resulted in superior and long-lasting antitumor activity. Altogether, we uncover that mitochondrial pyruvate uptake instructs metabolic flexibility for guiding T cell differentiation and antitumor responses.

[Nature Communications] Investigators showed that negative elongation factor (NELF), an RNA polymerase II pausing factor, cooperated with T cell factor 1 in T cell responses to cancer.

[Heredity] The authors discuss the recent advances in the understanding of the key mechanisms controlling the expression of immune checkpoint genes in tumour cells.