T-Helper 1 Immune Response in Metastatic Lymph Nodes of Pancreatic Ductal Adenocarcinoma: A Marker For Prolonged Survival

Nizri, Eran; Sternbach, Neta; Bar-David, Shoshi; Ben-Yehuda, A.; Gerstenhaber, Fabian; Ofir, Tali; Wolf, Ido; Weiner, Gilad; Lahat, Guy; Klausner, Joseph M.

doi:10.1245/s10434-017-6237-0

Cited by 12 publications

(7 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the lack of progression of low grade dysplasia in KCI mice is likely due to disruption of autophagy and immune suppression that are required for progression of Kras G12D -driven pancreatic lesions to PDAC [50,82,83]. We further demonstrated that high PRKCI expression in PDAC is associated with reduced activation of several immune signaling pathways implicated in the improved survival of PDAC cancer patients, including OX40, iCOS, and Th1 signaling [84][85][86][87].…”

Section: Discussionmentioning

confidence: 70%

Prkci Regulates Autophagy and Pancreatic Tumorigenesis in Mice

Inman

Liu

Buzhardt

et al. 2022

Cancers

View full text Add to dashboard Cite

Protein kinase C iota (PKCi) functions as a bonafide human oncogene in lung and ovarian cancer and is required for KrasG12D-mediated lung cancer initiation and progression. PKCi expression is required for pancreatic cancer cell growth and maintenance of the transformed phenotype; however, nothing is known about the role of PKCi in pancreas development or pancreatic tumorigenesis. In this study, we investigated the effect of pancreas-specific ablation of PKCi expression on pancreatic cellular homeostasis, susceptibility to pancreatitis, and KrasG12D-mediated pancreatic cancer development. Knockout of pancreatic Prkci significantly increased pancreatic immune cell infiltration, acinar cell DNA damage, and apoptosis, but reduced sensitivity to caerulein-induced pancreatitis. Prkci-ablated pancreatic acinar cells exhibited P62 aggregation and a loss of autophagic vesicles. Loss of pancreatic Prkci promoted KrasG12D-mediated pancreatic intraepithelial neoplasia formation but blocked progression to adenocarcinoma, consistent with disruption of autophagy. Our results reveal a novel promotive role for PKCi in pancreatic epithelial cell autophagy and pancreatic cancer progression.

show abstract

Section: Discussionmentioning

confidence: 70%

Prkci Regulates Autophagy and Pancreatic Tumorigenesis in Mice

Inman

Liu

Buzhardt

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…6E ). The previously reported T helper (Th) 1 immune response could be used as a biological marker for immunotherapy in metastatic lymph nodes of PDAC [ 22 ]. Specifically, the interactions of Th1-mediated responses between immune cells and type 5 ductal cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Single-cell RNA transcriptome reveals the intra-tumoral heterogeneity and regulators underlying tumor progression in metastatic pancreatic ductal adenocarcinoma

Chen

et al. 2021

Cell Death Discov.

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is the most frequent and aggressive pancreatic tumor characterized by high metastatic risk and special tumor microenvironment. To comprehensively delineate the complex intra-tumoral heterogeneity and the underlying mechanism during metastatic lesions malignant progression, single-cell RNA sequencing (scRNA-seq) was employed. PCA and TSNE were used for dimensionality reduction analysis and cell clustering. Find All Markers function was used to calculate differential genes in each cluster, and Do Heatmap function was used to plot the distribution of differential genes in each cluster. GSVA was employed to assign pathway activity estimates to individual cells. Lineage trajectory progression was inferred by monocle. CNV status was inferred to compare the heterogeneity among patients and subtypes by infercnv. Ligand-receptor interactions were identified by CellPhoneDB, and regulons network of cells was analyzed by SCENIC. Through RNA-sequencing of 6236 individual cells from 5 liver metastatic PDAC lesions, 10 major cell clusters are identified by using unbiased clustering analysis of expression profiling and well-known cell markers. Cells with high CNV level were considered as malignant cells and pathway analyses were carried out to highlight intratumor heterogeneity in PDAC. Pseudotime trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. The complex cellular communication suggested potential immunotherapeutic targets in PDAC. Regulon network identified multiple candidates for promising cell-specific transcriptional factors. Finally, metastatic-related genes expression levels and signaling pathways were validated in bulk RNA Sequencing data. This study contributed a comprehensive single-cell transcriptome atlas and contributed into novel insight of intratumor heterogeneity and molecular mechanism in metastatic PDAC.

show abstract

“…Importantly, interferon gamma (IFN-γ) produced by T h 1 cells not only has direct effects on arresting cellular proliferation, promoting apoptosis, and reducing angiogenesis but also on improving CTL responses to robust antitumor immunity [17]. Notably, T h 1 immune responses in lymph nodes signify a protective effect in colon cancer patients [27] and can be considered a marker for prolonged survival in pancreatic ductal adenocarcinoma (PDAC) patients [28].…”

Section: T Cellsmentioning

confidence: 99%

Chemokines and their Receptors: Multifaceted Roles in Cancer Progression and Potential Value as Cancer Prognostic Markers

Thu

Lee

Cho

2020

Cancers

157

131

View full text Add to dashboard Cite

Chemokines are chemotactic cytokines that mediate immune cell chemotaxis and lymphoid tissue development. Recent advances have indicated that chemokines and their cognate receptors play critical roles in cancer-related inflammation and cancer progression. On the basis of these findings, the chemokine system has become a new potential drug target for cancer immunotherapy. In this review, we summarize the essential roles of the complex network of chemokines and their receptors in cancer progression. Furthermore, we discuss the potential value of the chemokine system as a cancer prognostic marker. The chemokine system regulates the infiltration of immune cells into the tumor microenvironment, which induces both pro- and anti-immunity and promotes or suppresses tumor growth and proliferation, angiogenesis, and metastasis. Increasing evidence indicates the promising prognostic value of the chemokine system in cancer patients. While CCL2, CXCL10, and CX3CL1/CX3CR1 can serve as favorable or unfavorable prognostic factors depending on the cancer types, CCL14 and XCL1 possess good prognostic value. Other chemokines such as CXCL1, CXCL8, and CXCL12 are poor prognostic markers. Despite vast advances in our understanding of the complex nature of the chemokine system in tumor biology, knowledge about the multifaceted roles of the chemokine system in different types of cancers is still limited. Further studies are necessary to decipher distinct roles within the chemokine system in terms of cancer progression and to validate their potential value in cancer prognosis.

show abstract

T-Helper 1 Immune Response in Metastatic Lymph Nodes of Pancreatic Ductal Adenocarcinoma: A Marker For Prolonged Survival

Abstract: Our data indicate an association between Th1-type immune response and increased survival. Future research is needed to exploit Th1 immune response as a biological marker for immunotherapy.

Cited by 12 publications

References 36 publications

Prkci Regulates Autophagy and Pancreatic Tumorigenesis in Mice

Prkci Regulates Autophagy and Pancreatic Tumorigenesis in Mice

Single-cell RNA transcriptome reveals the intra-tumoral heterogeneity and regulators underlying tumor progression in metastatic pancreatic ductal adenocarcinoma

Chemokines and their Receptors: Multifaceted Roles in Cancer Progression and Potential Value as Cancer Prognostic Markers

Contact Info

Product

Resources

About