Spatial single-cell profiling and neighbourhood analysis reveal the determinants of immune architecture connected to checkpoint inhibitor therapy outcome in hepatocellular carcinoma.

Background: The determinants of the response to checkpoint immunotherapy in hepatocellular carcinoma (HCC) remain poorly understood. The organisation of the immune response in the tumour microenvironment (TME) is expected to govern immunotherapy outcomes but spatial immunotypes remain poorly defined.

Objective: We hypothesised that the deconvolution of spatial immune network architectures could identify clinically relevant immunotypes in HCC.

High-dimensional profiling reveals Tc17 cell enrichment in active Crohn's disease and identifies a potentially targetable signature.

The immune-pathology in Crohn's disease is linked to dysregulated CD4+ T cell responses biased towards pathogenic TH17 cells. However, the role of CD8+ T cells able to produce IL-17 (Tc17 cells) remains unclear. Here we characterize the peripheral blood and intestinal tissue of Crohn's disease patients (n = 61) with flow and mass cytometry and reveal a strong increase of Tc17 cells in active disease, mainly due to induction of conventional T cells.

Exhaustion of CD39-Expressing CD8 T Cells in Crohn's Disease Is Linked to Clinical Outcome.

Background & Aims: Exhaustion of CD8 T cells has been suggested to inform different clinical outcomes in Crohn's disease, but detailed analyses are lacking. This study aimed to identify the role of exhaustion on a single-cell level and identify relevant CD8 T cell populations in Crohn's disease.

Methods: Blood and intestinal tissue from 58 patients with Crohn's disease (active disease or remission) were assessed for CD8 T cell expression of exhaustion markers and their cytokine profile by highly multiplexed flow and mass cytometry.

T-cell exhaustion and residency dynamics inform clinical outcomes in hepatocellular carcinoma.

Background & Aims: Despite recent translation of immunotherapies into clinical practice, the immunobiology of hepatocellular carcinoma (HCC), in particular the role and clinical relevance of exhausted and liver-resident T cells remain unclear. We therefore dissected the landscape of exhausted and resident T cell responses in the peripheral blood and tumor microenvironment of patients with HCC.

Methods: Lymphocytes were isolated from the blood, tumor and tumor-surrounding liver tissue of patients with HCC (n = 40, n = 10 treated with anti-PD-1 therapy).