scholarly journals Identification of STAT5A as drug screening biomarker and immune checkpoint inhibitor in stomach adenocarcinoma via comprehensive bioinformatics analysis

2020 ◽  
Author(s):  
tao lin ◽  
Shuang Wu ◽  
Jianwen Wen ◽  
Wentao Zhang
Keyword(s):  
Overall Survival ◽  
T Cells ◽  
Drug Screening ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Disease Free Survival ◽  
Genetic Alterations ◽  
Apoptosis Pathway ◽  
Immune Biomarkers

Abstract Background: Gastric cancer is one of the fatal diseases and the third leading cause of cancer-related deaths worldwide. Limited drugs or therapeutic methods could be applied for these patients, and their prognosis was poor median overall survival (OS) of about 10 months. Increasing evidences demonstrated STAT gene family as biomarkers for prognosis, immunotherapy and drug screening.Methods: The drug screening biomarker and immune checkpoint inhibitor among STAT family were explored with several online bioinformatics tools.Results: The level STAT1/3/5A were significantly increased in STAD tissues compared with normal tissues. Methylation could downregulate STAT family expression, except STAT4. STAT1/5A/5B/6 may functioned as biomarkers for the prognosis of STAD patients. amplification and mRNA high were the most common genetic alteration form, genetic alterations could affect the disease-free survival but not overall survival of STAD patients. STAT family were involved in the activation of apoptosis pathway, EMT pathway, and hormone ER pathways, and the inhibition of cell cycle pathway, and DNA damage response pathways. Moreover, STAT5A and STAT5B were related with the drug sensitivity. Immune infiltration revealed that STAT5A level showed significant correlation with the abundance of immune cells (CD8+ T cells, CD4+ T cells, Macrophage, Neutrphils and Dendritic cells) and the level immune biomarkers. Somatic copy number alterations of STAT5A could significantly inhibit immune cell infiltration.Conclusions: STAT5A act as drug screening biomarker and immune checkpoint inhibitor in STAD.

scholarly journals Deep immune profiling reveals targetable mechanisms of immune evasion in immune checkpoint inhibitor-refractory glioblastoma

2021 ◽  
Vol 9 (6) ◽  
pp. e002181
Author(s):  
Erin F Simonds ◽  
Edbert D Lu ◽  
Oscar Badillo ◽  
Shokoufeh Karimi ◽  
Eric V Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Cells ◽  
Immune Evasion ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Prolonged Survival ◽  
Tumor Associated Macrophages ◽  
The Brain ◽  
Immune Profiling

BackgroundGlioblastoma (GBM) is refractory to immune checkpoint inhibitor (ICI) therapy. We sought to determine to what extent this immune evasion is due to intrinsic properties of the tumor cells versus the specialized immune context of the brain, and if it can be reversed.MethodsWe used CyTOF mass cytometry to compare the tumor immune microenvironments (TIME) of human tumors that are generally ICI-refractory (GBM and sarcoma) or ICI-responsive (renal cell carcinoma), as well as mouse models of GBM that are ICI-responsive (GL261) or ICI-refractory (SB28). We further compared SB28 tumors grown intracerebrally versus subcutaneously to determine how tumor site affects TIME and responsiveness to dual CTLA-4/PD-1 blockade. Informed by these data, we explored rational immunotherapeutic combinations.ResultsICI-sensitivity in human and mouse tumors was associated with increased T cells and dendritic cells (DCs), and fewer myeloid cells, in particular PD-L1+ tumor-associated macrophages. The SB28 mouse model of GBM responded to ICI when grown subcutaneously but not intracerebrally, providing a system to explore mechanisms underlying ICI resistance in GBM. The response to ICI in the subcutaneous SB28 model required CD4 T cells and NK cells, but not CD8 T cells. Recombinant FLT3L expanded DCs, improved antigen-specific T cell priming, and prolonged survival of mice with intracerebral SB28 tumors, but at the cost of increased Tregs. Targeting PD-L1 also prolonged survival, especially when combined with stereotactic radiation.ConclusionsOur data suggest that a major obstacle for effective immunotherapy of GBM is poor antigen presentation in the brain, rather than intrinsic immunosuppressive properties of GBM tumor cells. Deep immune profiling identified DCs and PD-L1+ tumor-associated macrophages as promising targetable cell populations, which was confirmed using therapeutic interventions in vivo.

Abstract LB037:89ZED88082A PET imaging to visualize CD8+T cells in patients with cancer treated with immune checkpoint inhibitor

2021 ◽  
Author(s):  
Laura Kist de Ruijter ◽  
Pim P. van de Donk ◽  
Jahlisa S. Hooiveld-Noeken ◽  
Danique Giesen ◽  
Alexander Ungewickell ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Pet Imaging ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Patients With Cancer

scholarly journals Positive Programmed Cell Death-Ligand 1 Expression Predicts Poor Treatment Outcomes in Esophageal Squamous Cell Carcinoma Patients Receiving Neoadjuvant Chemoradiotherapy

2019 ◽  
Vol 8 (11) ◽  
pp. 1864 ◽  
Author(s):  
Huang ◽  
Lu ◽  
Wang ◽  
Chen ◽  
Lo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Complete Response ◽  
Hazard Ratio ◽  
Free Survival ◽  
Disease Free

Background: Programmed cell death-ligand 1 (PD-L1) is present in a subgroup of cancer patients who may be favorable targets for immune checkpoint inhibitor therapies. However, the significance of the PD-L1 expression in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy remains unclear. Methods: By means of PD-L1 immunohistochemistry 22C3 pharmDx assay, we evaluate the PD-L1 expression and its association with clinical outcome in 107 ESCC patients receiving neoadjuvant chemoradiotherapy. Results: Patients with positive PD-L1 expression have significantly lower pathological complete response rates (13% versus 32%; P = 0.036) than those with negative PD-L1 expression. Univariate survival analysis found that positive PD-L1 expression were correlated with poor overall survival (P = 0.004) and inferior disease-free survival (P < 0.001). In a multivariate analysis, positive PD-L1 expression was independently associated with the absence of a pathologically complete response (P = 0.044, hazard ratio: 3.542), worse overall survival (P = 0.006, hazard ratio: 2.017), and inferior disease-free survival (P < 0.001, hazard ratio: 2.516). Conclusions: For patients with ESCC receiving neoadjuvant chemoradiotherapy, positive PD-L1 expression independently predicts the poor chemoradiotherapy response and worse treatment outcome. Thus, our data suggests that PD-L1 may be an influential biomarker for prognostic classification and for immune checkpoint inhibitor therapies in ESCC patients receiving neoadjuvant chemoradiotherapy.

PS-025-Elevated tissue homing of monocytes and increased cytotoxic activity of CD8+ T-cells in immune checkpoint inhibitor-induced hepatitis

2019 ◽  
Vol 70 (1) ◽  
pp. e19-e20
Author(s):  
Cathrin L.C. Gudd ◽  
Tong Liu ◽  
Evangelos Triantafyllou ◽  
David J. Pinato ◽  
You Yone ◽  
...  
Keyword(s):  
T Cells ◽  
Cytotoxic Activity ◽  
Cd8 T Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor
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