scholarly journals Faculty Opinions recommendation of Selective inhibition of the p38 alternative activation pathway in infiltrating T cells inhibits pancreatic cancer progression.

2020 ◽  
Author(s):  
John Silke
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Cancer Progression ◽  
Selective Inhibition ◽  
Alternative Activation ◽  
Activation Pathway

scholarly journals Selective inhibition of the p38 alternative activation pathway in infiltrating T cells inhibits pancreatic cancer progression

2015 ◽  
Vol 21 (11) ◽  
pp. 1337-1343 ◽  
Author(s):  
Muhammad S Alam ◽  
Matthias M Gaida ◽  
Frank Bergmann ◽  
Felix Lasitschka ◽  
Thomas Giese ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Cancer Progression ◽  
Selective Inhibition ◽  
Alternative Activation ◽  
Activation Pathway

scholarly journals The clinical implication of CD45RA+ naive T cells and CD45RO+ memory T cells in advanced pancreatic cancer: A proxy for tumor biology and outcome prediction.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 196-196
Author(s):  
Junjie Hang ◽  
Lixia Wu ◽  
Kequn Xu
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Cancer Progression ◽  
Cox Regression ◽  
Memory T Cells ◽  
Tumor Biology ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Student’S T

196 Background: Naive and memory T cells play a pivotal role in solid tumor pathogenesis but their role in pancreatic cancer progression remains elusive. Thus, we aimed to investigate their clinical potential in advanced pancreatic cancer (APC). Methods: Flow cytometry was performed to evaluate the level of peripheral naive and memory T cells from APC patients. Interrelationships between naive, memory T cells and clinicopathological variables were evaluated using pearson’s correlation. The prognostic impact of naive and memory T cells were assessed by Kaplan-Meier analysis and Cox regression. The correlation between naive/memory T cells and tumor progression was investigated by Student’s t test. Results: CD4+ naive/memory ratio showed close correlations with hemoglobin, red blood cell (RBC), absolute neutrophil count (ANC) and platelet while CD8+ naive/memory ratio was correlated with hemoglobin, RBC and CEA. Higher baseline lever of CD4+CD45RO+/CD4+ was correlated with better overall survival (OS) (P = 0.036). Patients with CD4+ naive/memory ratio ≥ 0.36 had a poorer OS than those with CD4+ naive/memory ratio < 0.36 (P = 0.021). In addition, CD4+ naive/memory ratio showed independent prognostic impact (HR 1.427, 95%CI 1.033-1.973, P = 0.031). Furthermore, poorer clinical response was correlated with higher level of CD8+ naive/memory ratio after the third cycle of chemotherapy (P = 0.01). Besides, patients with an low level of CD8+ naive/memory ratio had longer progression-free survival (PFS) (P = 0.028). Conclusions: We propose CD4+ naive/memory ratio as a novel prognostic biomarker for APC. In addition, CD8+ naive/memory ratio can be a candidate marker for predicting PFS and the change of its level may reflect the progression of APC.

scholarly journals The CD94/NKG2C killer lectin-like receptor constitutes an alternative activation pathway for a subset of CD8+ T cells

2005 ◽  
Vol 35 (7) ◽  
pp. 2071-2080 ◽  
Author(s):  
Mónica Gumá ◽  
Lisa K. Busch ◽  
Laura I. Salazar-Fontana ◽  
Beatriz Bellosillo ◽  
Carles Morte ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Alternative Activation ◽  
Activation Pathway

Increased Intratumoral Interleukin 22 Levels and Frequencies of Interleukin 22–Producing CD4+ T Cells Correlate With Pancreatic Cancer Progression

Pancreas ◽  
2014 ◽  
Vol 43 (3) ◽  
pp. 470-477 ◽  
Author(s):  
Xuejun Xu ◽  
Yichen Tang ◽  
Shixiang Guo ◽  
Yi Zhang ◽  
Yi Tian ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Cancer Progression ◽  
Cd4 T Cells ◽  
Interleukin 22

scholarly journals Correction: The CD94/NKG2C killer lectin-like receptor constitutes an alternative activation pathway for a subset of CD8+ T cells (Vol. 35 (7) 2005, DOI 10.1002/eji.200425843)

2005 ◽  
Vol 35 (7) ◽  
pp. 2259-2259
Author(s):  
Mónica Gumá ◽  
Lisa K. Busch ◽  
Laura I Salazar-Fontana ◽  
Beatriz Bellosillo ◽  
Carles Morte ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Alternative Activation ◽  
Activation Pathway

scholarly journals PDIA6 promotes pancreatic cancer progression and immune escape through CSN5-mediated deubiquitination of β-catenin and PD-L1

Neoplasia ◽  
2021 ◽  
Vol 23 (9) ◽  
pp. 912-928
Author(s):  
Yihui Ma ◽  
Peiyi Xia ◽  
Zhengyang Wang ◽  
Jingjing Xu ◽  
Lan Zhang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Immune Escape

scholarly journals 453 Novel combination immunotherapy for boosting and priming immune responses in pancreatic cancer: strong anti-tumour effects with interleukin-15 and CD40 agonist treatment

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A480-A480
Author(s):  
Jonas Van Audenaerde ◽  
Elly Marcq ◽  
Bianca von Scheidt ◽  
Ashleigh Davey ◽  
Amanda Oliver ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Dendritic Cells ◽  
Natural Killer ◽  
Mouse Models ◽  
Cd8 T Cells ◽  
Tumour Growth ◽  
Immune Memory ◽  
Combination Immunotherapy ◽  
Interleukin 15

BackgroundWith the poorest 5-year survival of all cancers, improving treatment for pancreatic cancer is one of the biggest challenges in cancer research. In this era of combination immunotherapies, we sought to explore the potential of combining both priming and activation of the immune system. To achieve this, we combined a CD40 agonist with interleukin-15 and tested its potential in pancreatic cancer.MethodsTwo different mouse models of pancreatic cancer were used to assess the potential of this combination regimen. Therefore, effects on tumour growth kinetics and survival were charted. Differential effects on immune signatures was investigated using RNA sequencing. Functional immune subset involvement was tested using different immune depletion experiments and multicolour flow cytometry in different relevant immune sites. Immune memory was checked using re-challenge experiments.ResultsWe demonstrated profound reduction in tumour growth and increased survival of mice with the majority of mice being cured when both agents were combined, including an unprecedented dose reduction of CD40 agonist without losing any efficacy (fig 1). RNA sequencing analysis showed involvement of natural killer cell and T cell mediated anti-tumour responses and the importance of antigen-presenting cell pathways. This combination resulted in enhanced infiltration of tumours by both cytotoxic T cells and natural killer cells, as well as a striking increase in the ratio of CD8+ T cells over T regulatory cells. We also observed a significant increase in numbers of dendritic cells in tumour draining lymph nodes, particularly CD103+ dendritic cells with cross-presentation potential. A critical role for CD8+ T cells and involvement of natural killer cells in the anti-tumour effect was highlighted. Importantly, strong immune memory was established, with an increase in memory CD8+ T cells only when both interleukin-15 and the CD40 agonist were combined.Abstract 453 Figure 1Tumour kinetics and survival in Panc02 (left) and KPC (right) pancreatic cancer mouse modelsConclusionsWe demonstrated profound synergistic anti-tumour effects upon combination of CD40 agonist and interleukin-15 treatment in mouse models of pancreatic cancer. This preclinical data supports initiation of a first-in-human clinical trial with this combination immunotherapy strategy in pancreatic cancer.

scholarly journals Long noncoding RNA LINC00941 promotes pancreatic cancer progression by competitively binding miR-335-5p to regulate ROCK1-mediated LIMK1/Cofilin-1 signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jie Wang ◽  
Zhiwei He ◽  
Jian Xu ◽  
Peng Chen ◽  
Jianxin Jiang
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cell Lines ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Loss Of Function ◽  
Mesenchymal Transition

AbstractAn accumulation of evidence indicates that long noncoding RNAs are involved in the tumorigenesis and progression of pancreatic cancer (PC). In this study, we investigated the functions and molecular mechanism of action of LINC00941 in PC. Quantitative PCR was used to examine the expression of LINC00941 and miR-335-5p in PC tissues and cell lines, and to investigate the correlation between LINC00941 expression and clinicopathological features. Plasmid vectors or lentiviruses were used to manipulate the expression of LINC00941, miR-335-5p, and ROCK1 in PC cell lines. Gain or loss-of-function assays and mechanistic assays were employed to verify the roles of LINC00941, miR-335-5p, and ROCK1 in PC cell growth and metastasis, both in vivo and in vitro. LINC00941 and ROCK1 were found to be highly expressed in PC, while miR-335-5p exhibited low expression. High LINC00941 expression was strongly associated with larger tumor size, lymph node metastasis, and poor prognosis. Functional experiments revealed that LINC00941 silencing significantly suppressed PC cell growth, metastasis and epithelial–mesenchymal transition. LINC00941 functioned as a molecular sponge for miR-335-5p, and a competitive endogenous RNA (ceRNA) for ROCK1, promoting ROCK1 upregulation, and LIMK1/Cofilin-1 pathway activation. Our observations lead us to conclude that LINC00941 functions as an oncogene in PC progression, behaving as a ceRNA for miR-335-5p binding. LINC00941 may therefore have potential utility as a diagnostic and treatment target in this disease.

scholarly journals MIB1 upregulates IQGAP1 and promotes pancreatic cancer progression by inducing ST7 degradation

2021 ◽  
Author(s):  
Bin Zhang ◽  
Xiang Cheng ◽  
Sudong Zhan ◽  
Xin Jin ◽  
Tao Liu
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression
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