Search

Anandasabapathy and colleagues show that the inhibitory receptor PD-1 impacts the specification of tissue-resident memory T cells in the skin.

T cell exhaustion limits antitumor immune responses. Vignali and colleagues identify neuropilin-1 as a novel immune checkpoint that cell-intrinsically operates to limit memory cell formation and can be targeted to enhance antitumor responses.

Here the authors show thatMETTL9 enzyme sustains neural development in vertebrates by maintaining the secretory pathway, mainly independently of METTL9 catalytic activity. METTL9 loss in cells leads to Golgi fragmentation.

Here the authors present cyclic peptide-based AND-gated nanosensors to detect concomitant protease activity. These nanosensors improve detection specificity during immune checkpoint blockade therapy compared with off-tumour anti-viral immunity in a mouse model.

Here, the authors use computational screening and a chemogenetic analysis of transgenic mice to show that Gα_s-coupled G-protein-coupled receptors on exhausted CD8⁺ T cells are involved in suppression of effector functions and inhibition of the protective effects of immune checkpoint immunotherapy.

Recent studies have highlighted the importance of B cells and tertiary lymphoid structures (TLS) in the modulation of anti-tumor immune responses. Here, the authors characterize how HPV status influences the phenotype of tumor infiltrating B cells in patients with head and neck squamous cell carcinoma and demonstrate that TLS with germinal centres are associated with better survival.

Exhausted T cells are associated with inefficient viral clearance, tumor immunity and response to immunotherapy. Here the authors show CD8⁺ T cells in the pancreatic islets have a LAG3-promoted ‘restrained’ phenotype resembling exhausted cells but maintain effector functions, and LAG3 expression limits pathology in the nonobese diabetic mouse model of type 1 diabetes.

Neoantigen-specific T cells recognise neoantigen-MHC complexes on target tumour cells. Here, the authors describe a molecular mechanism by which the neoantigen Hsf2 p.K72N is recognised by a corresponding high affinity Hsf2 p.K72N-reactive T cell receptor, 47BE7, from the mouse melanoma line B16F10.

Regulatory T cells obstruct effective anti-cancer immune responses. Vignali and colleagues demonstrate that IL-10 production and IL-35 production by tumor-infiltrating regulatory T cells mediate differential and non-redundant suppressive effects on tumor-reactive cytotoxic T cells.

BATF is a transcription factor that is needed for IL-9 production by T helper 9 cells. Here the authors show that STAT5 is needed at the Il9 locus to enable BATF to function in this manner and that this interaction can reprogram other T helper subsets into IL-9 producing cells, thus regulating the immune response to disease.

The role of IL-9 in the tumor microenvironment and its effects on macrophages remains unclear. Here, the authors show that IL-9 promotes the expansion of pulmonary macrophages and that targeting the IL-9R/arginase 1 axis restricts tumor growth, thus identifying this cytokine pathway as a potential therapeutic target.

Acetylcholine–α9 nAChR signaling regulates thymic negative selection.

Allogeneic chimeric antigen receptor (CAR) T cells are capable of inducing graft-versus-host disease (GVHD) in recipients, yet this is not commonly seen in the clinic. Marcel van den Brink, Michel Sadelain and colleagues show that alloreactive CAR T cells have reduced effector function due to signaling through the CAR and T cell receptor, resulting in reduced GVHD, while the graft-versus-leukemia effect is maintained by non-alloreactive CAR T cells.

The tumor microenvironment (TME) has an important role in Head and Neck Squamous Cell Carcinoma (HNSCC) progression. Here, using single-cell RNA sequencing and multiplexed imaging, the authors report the cellular complexity of the TME in patients with HNSCC, exploring inflammatory status, stromal heterogeneity and immune checkpoint receptor-ligand interactions.

With the development of large scale single cell RNA-seq technology, population-scale scRNA-seq studies are emerging. Here, the authors develop BAMM-SC, a tool for clustering droplet-based scRNA-seq data from multiple individuals simultaneously.