Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 41722836

MIF-CD74 axis facilitates MDSC infiltration in the tumor microenvironment of pancreatic ductal adenocarcinoma.

Hironori Fukuda·Kosuke Arai·Eri Hashimoto·Keisuke Sekine·Yasuhito Arai·Nobuyoshi Hiraoka·Aya Hirata·Makiko Yamashita·Kenta Narumi·Ayaka Kikuchi·Eri Sawai·Yuria Sawada·Ayana Sunami·Yukihiro Mizoguchi·Ryoichi Sadahiro·Yukiko Aikawa·Yasuko Henmi·Genki Okumura·Eri Sugiyama·Mami Takahashi·Tatsuhiro Shibata·Yukari Nishito·Hideaki Mizuno·Satoshi Nara·Minoru Esaki·Shohei Koyama·Shigehisa Kitano·Teruhiko Yoshida·Atsushi Ochiai·Hiroyuki Tsunoda·Kazunori Aoki
View original source ↗Export metadata ↓

Abstract

Immune checkpoint inhibitors show insufficient efficacy against pancreatic ductal adenocarcinoma (PDAC). The tumor microenvironment (TME) has a remarkable influence on responsiveness to cancer immunotherapy. The aim of this study was to investigate immunosuppressive characteristics of TME in PDAC tissues. The flow cytometry (FCM) of PDAC surgical specimens revealed that the profile of tumor-infiltrating leukocytes was classified into myeloid cell- and T-cell-dominant subtypes; the myeloid subtype was associated with poorer patient outcomes. Myeloid-derived suppressor cells (MDSCs) showed the highest hazard ratio among various myeloid cell types. Single-cell RNA sequencing and FCM revealed that most MDSCs, but not lymphocytes, in PDAC tissues characteristically express CD74. Macrophage migration inhibitory factor (MIF), a CD74 ligand, was highly expressed in cancer-associated fibroblasts (CAFs) and cancer cells. Spatial transcriptomics demonstrated that the MIF-CD74+ myeloid cell interaction was recognized in CAF-dominant areas in PDAC tissue. CAFs expressing immune suppressor molecules such as MFAP5 and LRRC15 were consistent with MIF+ CAFs. Furthermore, MIF+ CAFs enhanced the migratory activity of MDSCs and promoted MDSC induction and activation. In the murine model, MDSCs were significantly increased in MIF-expressing PDAC tumors, as were CD74+ M-MDSCs per M-MDSC, confirming in vivo interaction between CD74 and MIF. MDSCs play a crucial role in creating an immunosuppressive TME in PDAC; the MIF-CD74 axis drives interactions between MDSCs and CAFs.

Explore related subjects

HumansMacrophage Migration-Inhibitory FactorsCarcinoma, Pancreatic DuctalMyeloid-Derived Suppressor CellsTumor MicroenvironmentAntigens, Differentiation, B-LymphocyteAnimalsPancreatic NeoplasmsIntramolecular OxidoreductasesHistocompatibility Antigens Class IIMiceCell Line, TumorCancer-Associated FibroblastsFemaleMaleGene Expression Regulation, NeoplasticCD74Cancer-associated fibroblastsMacrophage migration inhibitory factorMyeloid-derived suppressor cellsPancreatic ductal adenocarcinomaJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Hironori Fukuda, Kosuke Arai, Eri Hashimoto, Keisuke Sekine, Yasuhito Arai, Nobuyoshi Hiraoka, Aya Hirata, Makiko Yamashita, Kenta Narumi, Ayaka Kikuchi, Eri Sawai, Yuria Sawada, Ayana Sunami, Yukihiro Mizoguchi, Ryoichi Sadahiro, Yukiko Aikawa, Yasuko Henmi, Genki Okumura, Eri Sugiyama, Mami Takahashi, Tatsuhiro Shibata, Yukari Nishito, Hideaki Mizuno, Satoshi Nara, Minoru Esaki, Shohei Koyama, Shigehisa Kitano, Teruhiko Yoshida, Atsushi Ochiai, Hiroyuki Tsunoda, Kazunori Aoki. 2026-02-20. MIF-CD74 axis facilitates MDSC infiltration in the tumor microenvironment of pancreatic ductal adenocarcinoma.. https://doi.org/10.1016/j.canlet.2026.218348

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2027

Global Genomic Surveillance.

Global genomic surveillance has emerged as a foundational pillar of public health in the twenty-first century, enabling real-time tracking of pathogen evolution and informing outbreak response. This chapter examines the strategic architecture of global genomic surveillance, focusing on its application to arboviruses such as chikungunya virus (CHIKV). It explores the integration of genomic data with epidemiological, clinical, and environmental information within a One Health framework, while addressing critical challenges in governance, equity, and interoperability. The discussion covers the entire genomic surveillance workflow, from sample collection and sequencing to bioinformatic analysis and phylogenetic inference, and highlights the transformative role of artificial intelligence (AI) in predictive surveillance. By analyzing global initiatives, operational barriers, and emerging technologies, this chapter underscores the necessity of sustainable, equitable, and interoperable genomic systems to proactively address current and future infectious disease threats.

Humans↗
PubMed2027

Systematic Dissection of Key Driver Perturbation Signatures in Single Cells via ECCITE-seq.

CRISPR screens, such as expanded CRISPR-compatible cellular indexing of transcriptomes and epitopes by sequencing (ECCITE-seq), enable the simultaneous measurement of transcriptomes, gRNA identity, and cell-surface protein expression at single-cell resolution to systematically interrogate gene function. This platform provides a powerful and scalable experimental approach for validating disease-associated regulators identified by large-scale association studies and other computational methods, including network-based analyses of multi-omics data. Here, as an example application, we describe an ECCITE-seq framework to characterize the transcriptomic consequences of perturbing multiple neuronal key driver genes associated with Alzheimer's disease (AD) in human-induced pluripotent stem cell (hiPSC)-derived neurons. More broadly, by integrating customized pooled gRNA libraries with different CRISPR effectors across multiple cell types, this approach allows for the assessment of the regulatory impact of candidate genes implicated in development and disease processes.

Humans↗
PubMed2027

Identification of Genome-Wide Chromatin Structural Aberration in Cancer by Hi-C Analysis.

Aberrant three-dimensional genome organization is a hallmark of cancer, often driving oncogene activation through mechanisms such as enhancer hijacking. High-throughput chromosome conformation capture (Hi-C) maps these interactions on a genome-wide scale. Unlike earlier dilution-based methods, in situ Hi-C performs proximity ligation within intact nuclei, minimizing random ligation noise and enabling fine-scale structure detection. This chapter describes an optimized in situ Hi-C protocol tailored for cancer cell lines using MboI digestion and biotin-mediated pull-down to generate high-complexity libraries. We further outline a computational workflow that extends beyond standard topological mapping of compartments and topologically associating domains to identify cancer-specific aberrations. Specifically, we focus on detecting chromosomal rearrangements (structural variants) and characterizing the distinct circular topology of extrachromosomal DNA. This integrated experimental and analytical framework provides the necessary tools to dissect the spatial dysregulation underlying tumor evolution.

Humans↗