M2 macrophage + Pancreatic cancer

INTRODUCTION: Pancreatic adenocarcinoma (PDAC) is an aggressive tumor with limited response to both chemotherapy and immunotherapy. Pre-treatment tumor features within the tumor immune microenvironment (TiME) may influence treatment response. We hypothesized that the pre-treatment TiME composition differs between metastatic and primary lesions and would be associated with response to modified FOLFIRINOX (mFFX) or gemcitabine-based (Gem-based) therapy. METHODS: Using RNAseq data from a cohort of treatment-naïve, advanced PDAC patients in the COMPASS trial, differential gene expression analysis of key immunomodulatory genes in were analyzed based on multiple parameters including tumor site, response to mFFX, and response to Gem-based treatment...

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a challenging target for immunotherapy because it has an immunosuppressive tumor microenvironment. Neoadjuvant chemoradiotherapy can increase tumor-infiltrating lymphocyte (TIL) density, which may predict overall survival (OS). We hypothesized that adding programmed cell death protein 1 (PD-1) blockade to chemoradiotherapy would be well tolerated and increase TILs among patients with localized PDAC. METHODS: Patients were randomized 2:1 to Arm A (receiving pembrolizumab plus chemoradiotherapy (capecitabine and external beam radiation)) or Arm B (receiving chemoradiotherapy alone) before anticipated pancreatectomy...

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with a poor prognosis, and effective treatments for PDAC are lacking. In this study, we hypothesized that miR-506 promotes antitumor immune response in PDAC by reprogramming tumor-associated macrophages toward an M1 phenotype to reverse its immunosuppressive tumor microenvironment (TME). First, the relationship between TME and the expression of miR-506 was assessed using clinical samples. Our results provided evidence that lower expression of miR-506 was associated with poor prognosis and immunosuppressive TME in PDAC patients...

Background: Exosomes and cancer immunology are both important areas of research for cancer treatment. As much effort has been made to explore the relationship between exosomes and cancer immunology, exosomes in cancer immunology have become a hotspot in medical research. Methods: We retrieved all relevant publications between 2011 and 2021 from the Web of Science and utilized Microsoft Excel 365, Citespace, Online Analysis Platform of Literature Metrology (https://bibliometric.com/) and software including VOS viewer to analyze and visualize the research result...

UNLABELLED: Axon guidance molecules were found to be the gene family most frequently altered in pancreatic ductal adenocarcinoma (PDA) through mutations and copy number changes. However, the exact molecular mechanism regarding PDA development remained unclear. Using genetically engineered mouse models to examine one of the axon guidance molecules, semaphorin 3D (SEMA3D), we found a dual role for tumor-derived SEMA3D in malignant transformation of pancreatic epithelial cells and a role for nerve-derived SEMA3D in PDA development...

PURPOSE: Using a real-world database with matched genomic-transcriptomic molecular data, we sought to characterize the distinct molecular correlates underlying clinical differences between patients with young-onset pancreatic cancer (YOPC; younger than 50 years) and patients with average-onset pancreatic cancer (AOPC; 70 years and older). METHODS: We analyzed matched whole-transcriptome and DNA sequencing data from 2,430 patient samples (YOPC, n = 292; AOPC, n = 2,138) from the Caris Life Sciences database (Phoenix, AZ)...

This study examined the composition of the immune microenvironment at different sites within resected pancreas specimens from patients with pancreatic ductal adenocarcinoma (PDAC). Therefore, single-cell suspensions were made from fresh tumor and non-tumorous tissue. Fourteen patients were included from whom twelve PDAC and five non-tumorous samples were obtained. These samples were analyzed with a nineteen marker panel on the Aurora spectral flow cytometer. Furthermore, slides from formalin-fixed paraffine PDACs of eight additional patients were stained with eight markers and analyzed by multispectral imaging...

INTRODUCTION: OAS1(2'-5'-oligoadenylate synthetase 1) is a member of the Interferon-Stimulated Genes which plays an important role in the antiviral process. In recent years, the role of OAS1 in tumors has attracted attention, and it was found to be associated with prognosis in several tumors. However, the mechanism by which OAS1 affects tumors is unclear and pan-cancer study of OAS1 is necessary to better understand its implication in cancers. METHODS: The expression, prognostic value, genetic alteration, alternative splicing events of OAS1 in pan-cancers were analyzed using TCGA, GTEx, HPA, GEPIA and OncoSplicing databases...

BACKGROUND: Pancreatic cancer is a highly lethal disease with no effective treatments. Lactobacillus casei (L. casei) and Lactobacillus reuteri (L. reuteri) exhibited therapeutic effects on several cancers, but their roles in pancreatic cancer are unknown. This study aims to explore how L. casei & L. reuteri influence pancreatic cancer and the underlying mechanisms. METHODS: Pancreatic cancer cells were treated with L. casei & L. reuteri and co-cultured with macrophages in a transwell system in vitro...

Tumor-associated macrophages (TAMs), as a major and essential component of tumor microenvironment (TME), play a critical role in orchestrating pancreatic cancer (PaC) tumorigenesis from initiation to angiogenesis, growth, and systemic dissemination, as well as immunosuppression and resistance to chemotherapy and immunotherapy; however, the critical intrinsic factors responsible for TAMs reprograming and function remain to be identified. By performing single-cell RNA sequencing, transforming growth factor-beta-induced protein (TGFBI) was identified as TAM-producing factor in murine PaC tumors...

Acetaldehyde dehydrogenases (ALDH) 1B1 is associated with a poor prognosis in pancreatic cancer, colorectal cancer, and osteosarcoma. Overexpression of ALDH also impairs tumor immunity. However, it is unclear how ALDH1B1 is associated with patient prognosis and immune infiltration in different cancer types. This is an original research based on bioinformatics analysis. In this study, we investigated the expression and prognostic value of ALDH1B1 in pan-cancer specimens using several databases, including GEPIA2 and Kaplan-Meier Plotter...

Background: The extremely malignant tumour known as pancreatic cancer (PC) lacks efficient prognostic markers and treatment strategies. The microbiome is crucial to how cancer develops and responds to treatment. Our study was conducted in order to better understand how PC patients' microbiomes influence their outcome, tumour microenvironment, and responsiveness to immunotherapy. Methods: We integrated transcriptome and microbiome data of PC and used univariable Cox regression and Kaplan-Meier method for screening the prognostic microbes...

The CD200 is a cell membrane protein expressed by tumor cells, and its receptor CD200 receptor (CD200R) is expressed by immune cells including macrophages and dendritic cells. The formation of CD200-CD200R inhibits the cellular functions of the targeted immune cells, so CD200 is one type of the immune checkpoint and blockade CD200-CD200R formation is a potential cancer treatment. However, the CD200 blockade has opposite treatment outcomes in different types of cancers. For instance, the CD200R deficient mice have a higher tumor load than the wild type (WT) mice in melanoma suggesting that CD200-CD200R inhibits melanoma...

BACKGROUND: This study investigates sex disparities in clinical outcomes and tumour immune profiles in patients with pancreatic ductal adenocarcinoma (PDAC) who underwent upfront resection or resection preceded by gemcitabine-based neoadjuvant chemoradiotherapy (nCRT). METHODS: Patients originated from the PREOPANC randomised controlled trial. Upfront surgery was performed in 82 patients, and 66 received nCRT before resection. The impact of sex on overall survival (OS) was investigated using Cox proportional hazards models...

Alcohol dehydrogenase (ADH) oxidizes alcohol into acetaldehyde (AA), which is a known carcinogen. Aldehyde dehydrogenase (ALDH) oxidizes AA into acetate. Therefore, pancreatic cancer that expresses a high level of ADH1B that generates more AA is expected to be associated with aggressive cancer. On the other hand, given that the differentiated cells that retain their cellular functions typically exhibit lower proliferation rates, it remains unclear whether pancreatic adenocarcinoma (PDAC) with high ADH1B gene expression is linked to aggressive features in patients...

Objective: This study clarified the risk factors and pathophysiology of pancreatic cancer by examining the factors associated with fatty pancreas. Methods: The degree of fatty pancreas, background factors, and incidence of pancreatic cancer were examined among nonalcoholic fatty liver disease (NAFLD) patients (n = 281) and intraductal papillary mucinous neoplasm (IPMN) patients with a family history of pancreatic cancer (n = 38). The presence of fatty pancreas was confirmed by the pancreatic CT value/splenic CT value ratio (P/S ratio)...

During development of pancreatic cancer macrophage-mediated inflammatory processes and the formation of cancerous lesions are tightly connected. Based on insight from mouse models we provide an overview on the functions of classically-activated pro-inflammatory and alternatively-activated anti-inflammatory macrophages in the initiation and progression of pancreatic cancer. We highlight their roles in earliest events of tumor initiation such as acinar-to-ductal metaplasia (ADM), organization of the fibrotic lesion microenvironment, and growth of low-grade (LG) lesions...

Bulk analyses of pancreatic ductal adenocarcinoma (PDAC) samples are complicated by the tumor microenvironment (TME), i.e. signals from fibroblasts, endocrine, exocrine, and immune cells. Despite this, we and others have established tumor and stroma subtypes with prognostic significance. However, understanding of underlying signals driving distinct immune and stromal landscapes is still incomplete. Here we integrate 92 single cell RNA-seq samples from seven independent studies to build a reproducible PDAC atlas with a focus on tumor-TME interdependence...

Tumor-associated macrophages M2 (TAM2), which are highly prevalent infiltrating immune cells in the stroma of pancreatic cancer (PC), have been found to induce an immunosuppressive tumor microenvironment, thus enhancing tumor initiation and progression. However, the immune therapy response and prognostic significance of regulatory genes associated with TAM2 in PC are currently unknown. Based on TCGA transcriptomic data and single-cell sequencing data from the GEO database, we identified TAM2-driven genes using the WGCNA algorithm...

Here, we fabricated nanoparticles made solely from the membrane of cells found in the pancreatic tumour's microenvironment (TME), like the human MiaPaCa-2 cells and M2-polarized macrophages. The cell membrane-derived nanoparticles (CMNPs) deriving from the MiaPaCa-2 cells (MPC2-CMNPs) were loaded with the chemotherapeutic drug paclitaxel (PTX), and the CMNPs deriving from M2-polarized macrophages (M2-CMNPs) were loaded with the colony-stimulating factor 1 receptor inhibitor, pexidartinib (PXDB). The CMNPs' thorough morphological and physicochemical characterisation was followed by an in-depth study of their targeting ability and the endocytosis pathway involved during their internalisation...