GSE132959 Systematic identification of immunotherapy targets using genome-scale in vivo CRISPR screens in CD8+ cytotoxic T cells scRNA-Seq

Contributors : Ryan D Chow ; Sidi ChenSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusCD8+  cytotoxic T cells play essential roles in anti-tumor immune responses. Here, we performed in vivo screens in CD8+ T cells and identified regulators of tumor infiltration and killing, which are directly relevant to cancer immunotherapy. Unlike in vitro screens, the in vivo screen robustly re-ident ified canonical immunotherapy targets such as PD-1 and Tim-3, along with genes that have not been characterized in T cells. The infiltration and degranulation screens converged on an RNA helicase Dhx37. Dhx37 knockout enhanced the efficacy of antigen-specific CD8+ T cells against cancer in vivo. Im munological characterization in mouse and human CD8+ T cells revealed that DHX37 suppresses effector function, cytokine production, and T cell activation. Transcriptomic profiling and biochemical interrogation revealed a role for DHX37 in modulating the NF-kB pathway. These data demonstrated the po wer of high-throughput in vivo genetic screens for immunotherapy target discovery, and uncovered DHX37 as a functional regulator of CD8+ T cells.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research

Related Links:

Authors: Ahmed SR, Petersen E, Patel R, Migden MR Abstract INTRODUCTION: In September of 2018, the United States Federal Drug Administration (FDA) approved cemiplimab-rwlc (Libtayo) for advanced cutaneous squamous cell carcinoma (CSCC). Cemiplimab is an intravenous human monoclonal antibody directed against programmed cell death-1 receptor (PD-1). Cemiplimab blocks T-cell inactivation and enhances the immune system's anti-tumor response. Areas Covered: We review CSCC and the studies leading to cemiplimab's approval, including common side effects and safety issues experienced during the clinical trials. Expert Opini...
Source: Expert Review of Clinical Pharmacology - Category: Drugs & Pharmacology Tags: Expert Rev Clin Pharmacol Source Type: research
Conditions:   Hepatocellular Carcinoma;   Hepatoblastoma Interventions:   Genetic: TEGAR T cells;   Drug: Cytoxan;   Drug: Fludarabine Sponsors:   Baylor College of Medicine;   Texas Children's Hospital;   The Methodist Hospital System Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Chimeric antigen receptor (CAR) T cell therapies are used to treat cancer, engineering T cells to be more aggressive towards cancer cells. The approach has proven quite effective in comparison to past treatments for a number of cancer types. In principle this CAR-T immunotherapy can be used to target any cell population that has distinct surface markers, not just cancer cells. Here, researchers demonstrate the ability to destroy the fibroblasts responsible for generating fibrosis in the aging heart. Fibrosis is a form of dysregulated tissue maintenance, in which cells build up scar-like deposits of collagen that degrade ti...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
A trial of the gadget in Holland found it could detect the PD-L1 protein by patients simply breathing into it. PD-L1 is thought to dampen and weaken the immune system when cancer hits.
Source: the Mail online | Health - Category: Consumer Health News Source Type: news
Conclusion: Taken together, we performed a comprehensive evaluation of the immune landscape of IDC and constructed an immune signature related to the immune landscape. This analysis of TME immune infiltration landscape has shed light on how IDC respond to immunotherapy and may guide the development of novel drug combination strategies.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Adding radiation after progression on immunotherapy increased progression-free survival in some patients.Medscape Medical News
Source: Medscape Medical News Headlines - Category: Consumer Health News Tags: Hematology-Oncology News Source Type: news
The efficacy of third generation anti‑HER2 chimeric antigen receptor T cells in combination with PD1 blockade against malignant glioblastoma cells. Oncol Rep. 2019 Aug 05;: Authors: Shen L, Li H, Bin S, Li P, Chen J, Gu H, Yuan W Abstract Without effective treatment, glioblastoma is one of the deadliest cancers worldwide. The aim of the present study was to explore whether combinational immunotherapy is effective for treating malignant glioblastoma in vitro. The therapeutic efficacy of third generation anti‑human epidermal growth factor receptor 2 (HER2) chimeric antigen receptor (CAR)‑T cel...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
Development of c‑MET‑specific chimeric antigen receptor‑engineered natural killer cells with cytotoxic effects on human liver cancer HepG2 cells. Mol Med Rep. 2019 Jul 25;: Authors: Liu B, Liu ZZ, Zhou ML, Lin JW, Chen XM, Li Z, Gao WB, Yu ZD, Liu T Abstract In recent years, cellular immunotherapy has served an important role in the combined treatment of hepatocellular carcinoma. The possibility of specific cell therapies for the treatment of solid tumours has been further explored following the success of chimeric antigen receptor (CAR)‑T cell therapy in the treatment of haematological tumours...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
Studies show that targeted agents and immunotherapy may prove to be effective treatments.Medscape Oncology
Source: Medscape Hematology-Oncology Headlines - Category: Cancer & Oncology Tags: Hematology-Oncology Article Source Type: news
Nature Reviews Clinical Oncology, Published online: 17 September 2019; doi:10.1038/s41571-019-0276-3The presence and prognostic relevance of the intratumoural microbiota in pancreatic cancer, and the roles of intratumoural bacteria in oncogenesis and therapeutic response are beginning to be elucidated. The feasibility of characterizing intratumoural microbial communities from paraffin-embedded tissues has now been validated, providing greater opportunities for retrospective research. Prospective studies are also needed to test the efficacy of rational approaches combining microbial modulation with chemotherapy and/or immunotherapy.
Source: Nature Reviews Clinical Oncology - Category: Cancer & Oncology Authors: Source Type: research
More News: Cancer | Cancer & Oncology | Genetics | Immunotherapy