Evidence map›Paper›PMID 42421015›Full record

ArticleMolecular cancer2026

Systemic immunosuppression limits NK cell therapy efficacy in pancreatic cancer.

Chunbo He, Dezhen Wang, Tuo Hu, Daisy Gonzalez, Ravi Thakur, Damian P Matysniak, Ryan J King, Sai Sundeep Kollala, Spas Dimitrov Markov, Yuki Fujii and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer, 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

22 authors.

Chunbo He *Department of Oncology Science, University of Oklahoma Health Campus, 940 Stanton L. Young Blvd., BMSB 332, Oklahoma City, OK, 73104, USA.
Dezhen Wang *Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Tuo HuEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Daisy GonzalezEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Ravi ThakurDepartment of Oncology Science, University of Oklahoma Health Campus, 940 Stanton L. Young Blvd., BMSB 332, Oklahoma City, OK, 73104, USA.
Damian P MatysniakDepartment of Oncology Science, University of Oklahoma Health Campus, 940 Stanton L. Young Blvd., BMSB 332, Oklahoma City, OK, 73104, USA.
Ryan J KingEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Sai Sundeep KollalaEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Spas Dimitrov MarkovEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Yuki FujiiDepartment of Oncology Science, University of Oklahoma Health Campus, 940 Stanton L. Young Blvd., BMSB 332, Oklahoma City, OK, 73104, USA.
Gullanki Naga Venkata Charan TejDepartment of Oncology Science, University of Oklahoma Health Campus, 940 Stanton L. Young Blvd., BMSB 332, Oklahoma City, OK, 73104, USA.
Junzhang ZhaoDepartment of Oncology Science, University of Oklahoma Health Campus, 940 Stanton L. Young Blvd., BMSB 332, Oklahoma City, OK, 73104, USA.
Longyang JinDepartment of Oncology Science, University of Oklahoma Health Campus, 940 Stanton L. Young Blvd., BMSB 332, Oklahoma City, OK, 73104, USA.
Rebecca Oberley-DeeganDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Surendra K ShuklaDepartment of Oncology Science, University of Oklahoma Health Campus, 940 Stanton L. Young Blvd., BMSB 332, Oklahoma City, OK, 73104, USA.
Xin A ZhangDepartment of Biochemistry and Physiology, University of Oklahoma Health Campus, Oklahoma City, OK, 73104, USA.
Jacob E FriedmanHarold Hamm Diabetes Center, University of Oklahoma Health Campus, Oklahoma City, OK, 73117, USA.
Pankaj K SinghDepartment of Oncology Science, University of Oklahoma Health Campus, 940 Stanton L. Young Blvd., BMSB 332, Oklahoma City, OK, 73104, USA.
Michael A HollingsworthEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Marina Pasca di MaglianoDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Howard C CrawfordDepartment of Pharmacology and Toxicology, Michigan State University, Lansing, MI, USA.
Kamiya MehlaDepartment of Oncology Science, University of Oklahoma Health Campus, 940 Stanton L. Young Blvd., BMSB 332, Oklahoma City, OK, 73104, USA. kamiya-mehla@ouhsc.edu.

Funding

Tissue Core-UNMC Rapid Autopsy ProgramU54CA274329 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Pankaj Kumar Singh · 2022 to 2026
$7.8M
Targeting Tumor-Stromal Metabolic Cross-Talk in Pancreatic CancerR01CA163649 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Pankaj Kumar Singh · 2012 to 2026
$5.4M
Vitamin B6 Modulates NK Cell Metabolism in Pancreatic CancerR37CA276924 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Kamiya Mehla · 2023 to 2026
$1.5M
Department of Defense HT9425-23-1-1001HHDC-SCC Team Science pilot grant 20007993National Institutes of Health grant R01CA163649National Institutes of Health grant R37CA276924NCI NIH HHS R01 CA163649NCI NIH HHS R37 CA276924NCI NIH HHS U54 CA274329NIH HHS U54CA274329
6 · The paper itself

Abstract

Nature killer (NK) cell plays a critical role in cancer immunosurveillance and is considered a potent immunotherapeutic tool for many cancers, including pancreatic ductal adenocarcinomas (PDACs). Increasing evidence suggests that cancer occurs with systemic immune perturbations. However, the effects of PDAC tumor burden on systemic NK cells remain poorly understood. PDAC tumor-bearing mice display decreased frequency and dysfunction of NKs the spleens. We identified an increase in Gr-1+ myeloid cells within the spleens, which negatively impacts both endogenous and adoptively transferred NK cell frequency and function. Apolipoprotein E (ApoE), a lipid metabolism regulator, is upregulated in Gr-1+ myeloid cells of tumor-bearing mice, promoting lipid oxidation and reactive oxygen species (ROS) generation. Genetic knockout of Apoe in Gr-1+ myeloid cells abrogate their suppressive effects on NK cell function. Furthermore, treatment with lipid metabolism inhibitors restores endogenous and adoptively transferred NKs' effector function in the spleens and tumor microenvironment. These studies underscore the importance of understanding preexisting systemic alterations in PDAC patients before applying NK cell-based immunotherapies.

Indexed as

Immunosuppression TherapyKiller Cells, NaturalPancreatic NeoplasmsAnimalsApolipoproteins ECarcinoma, Pancreatic DuctalCell Line, TumorDisease Models, AnimalHumansImmunotherapyLipid MetabolismMiceReactive Oxygen SpeciesTumor MicroenvironmentApolipoproteins EReactive Oxygen SpeciesApolipoprotein E (ApoE)ImmunotherapiesLipid oxidationLipid peroxidationMyeloid-derived suppressive cells (MDSCs)NK cellsPancreatic ductal adenocarcinomas (PDAC)

Identifiers

PMID42421015
PMCPMC13355361

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.