Investigating the NASH-triggered HCC in the context PD-1-targeted immunotherapy with flow cytometry, single cell RNA sequencing, immunohistochemistry and mass spectrometric analyses, we found a progressive increase of CD8+PD-1+ effector T-cells with a unique profile of exhaustion and activation markers rising with murine and human NASH severity. Notably, late-stage HCC treatment with PD-1-targeted...

Summary from the GEO: "Whereas some cancer types (e.g. melanoma) can be efficiently treated with immunotherapy, others lack measurable positive effects (e.g. PDAC ). Moreover, stratification of responders/non-responders is only possible in some cancer types (e.g. melanoma). Hepatocellular carcinoma (HCC) has a dismal prognosis, limited treatment options and survival benefit, and represents a potential...

Summary from the GEO: "Hepatocellular carcinoma (HCC) has dismal treatment responses to systemic therapies and is caused by both, viral and non-viral etiologies, including non-alcoholic steatohepatitis (NASH) 1–5. NASH - triggered by high caloric intake and sedentary lifestyle - has become an important driver for HCC development. Immunotherapy has been recently approved for HCC but stratification...

Summary from the ENA: "Mice with advanced non alcoholic fatty liver disease (NASH) by dietary feeding regime of choline deficient high fat diet (CD-HFD) were treated with antibodies (a-CD8 depletion; a-PD1 checkpoint inhibition; Co-depletion by a-CD8 and a-NK1.1 administration) for 8 weeks. Surprisingly, a-CD8 depletion prevented hepatocarcinogenesis; in contrast a-PD1 checkpoint inhibition induced...

Summary from GEO: "Natural Killer (NK) cells and CD8+ T cells share many characteristics at steady state and during viral infection. In this study, we interrogate the metabolic pathways that fuel NK cell effector function in response to mouse cytomegalovirus (MCMV) infection. This dataset contains transcriptional profiling of wild-type and LDHA-deficient Ly49Hpositive NK cells at steady state and...

Study Description from dbGaP: Desmoplastic melanoma (DM) is a rare subtype of melanoma characterized by dense fibrous stroma, resistance to chemotherapy and a lack of actionable driver mutations, but is highly associated with ultraviolet light DNA damage. We analysed 60 patients with advanced DM treated with programmed cell death 1 (PD-1) or PD-1 ligand (PD-L1) blocking antibody therapy. Objective...

Summary from the GEO: "The paradox of tumor immunology is that tumor infiltrating lymphocytes (TILs) are dysfunctional in situ and yet are capable of stem cell-like behavior with self-renewal, massive expansion, multipotency, and eradication of large metastatic tumors. Here we report that the overabundance of potassium in the tumor microenvironment (TME) can explain both phenomena." Overall design...

Summary from the GEO: "CD4+ and CD8+ T cells can reciprocally differentiate into Th/Tc1, Th/Tc17 and Th/Tc22. Although alloreactive Th/Tc1 cells play a critical role in initiating pathogenesis of gut acute graft-versus-host disease (Gut-aGVHD), the pathogenic T cells in steroid-resistant Gut-aGVHD (SR-Gut-aGVHD) remains unclear. Here, we show that in murine models of SR-Gut-aGVHD, the pathogenesis...

Summary from the GEO: "CD4+ and CD8+ T cells can reciprocally differentiate into Th/Tc1, Th/Tc17 and Th/Tc22. Although alloreactive Th/Tc1 cells play a critical role in initiating pathogenesis of gut acute graft-versus-host disease (Gut-aGVHD), the pathogenic T cells in steroid-resistant Gut-aGVHD (SR-Gut-aGVHD) remains unclear. Here, we show that in murine models of SR-Gut-aGVHD, the pathogenesis...

Summary from the GEO: "Success of immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC) has invigorated their use in neo-adjuvant setting for early-stage disease. However, the cellular and molecular mechanisms of the early immune responses to therapy remain poorly understood. Through an integrated analysis of early-stage NSCLC patients and a Kras-mutant mouse model, we show a...