Evidence map›Paper›PMID 42877588›Full record

ReviewFrontiers in immunology2026

Innate immunity-stroma crosstalk in pancreatic cancer: overcoming spatial and metabolic barriers to immunotherapy.

Yulong Hou, Zhenhua Tan

Abstract readReview
In one paragraph

Review in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Yulong HouHuzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, Zhejiang, China.
Zhenhua TanHuzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, Zhejiang, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) exhibits profound resistance to current immunotherapies, a challenge largely attributed to its uniquely immunosuppressive and desmoplastic tumor microenvironment (TME). At the heart of this therapeutic recalcitrance lies the dynamic, bidirectional crosstalk between innate immune cells-particularly tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs)-and stromal components, notably cancer-associated fibroblasts (CAFs). This review comprehensively delineates how the innate immunity-stroma axis establishes formidable spatial and metabolic barriers that thwart effective antitumor immunity. Spatially, dense collagen matrices, periductal fibroblast organization, and neutrophil extracellular traps (NETs) create physical checkpoints that exclude cytotoxic CD8+ T cells and natural killer (NK) cells from tumor nests. Metabolically, elevated lactate, cholesterol dysregulation, adenosine accumulation, and altered polyamine metabolism synergistically paralyze effector lymphocytes while driving immunosuppressive myeloid polarization. We highlight the key molecular networks orchestrating this pathological crosstalk, including the NF-κB, IL-1β, JAK/STAT3, and TGF-β signaling pathways. Furthermore, we summarize emerging therapeutic strategies designed to dismantle these barriers, encompassing macrophage reprogramming, CAF modulation, and metabolic interventions. Finally, we discuss the multidimensional "3D+R" framework-integrating de-desmoplasia, de-adenosine,

Indexed as

Carcinoma, Pancreatic DuctalImmunity, InnateImmunotherapyPancreatic NeoplasmsStromal CellsTumor MicroenvironmentAnimalsCancer-Associated FibroblastsHumansSignal TransductionTumor-Associated Macrophagescancer-associated fibroblasts (CAFs)immunotherapy resistanceinnate immunitypancreatic ductal adenocarcinoma (PDAC)tumor microenvironment (TME)

Identifiers

PMID42877588
PMCPMC13662915

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.