Evidence mapPaperPMID 33513866Full record

ArticleCancers2021

DPP4 Inhibitor Sitagliptin Enhances Lymphocyte Recruitment and Prolongs Survival in a Syngeneic Ovarian Cancer Mouse Model.

Amy L Wilson, Laura R Moffitt, Kirsty L Wilson, Maree Bilandzic, Mark D Wright, Mark D Gorrell, Martin K Oehler, Magdalena Plebanski, Andrew N Stephens

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.2field-weighted citation impact, top 9% of its field
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

17 citing papers in PubMed, 31 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Review
  5. Review
  6. Obesity-Associated Colorectal Cancer.International journal of molecular sciences · 2024
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. CD26 and Cancer.Cancers · 2022
    Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
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

9 authors at 5 institutions in 1 country.

Amy L WilsonCentre for Cancer Research, Hudson Institute of Medical Research, Clayton 3168, Australia.
Laura R MoffittCentre for Cancer Research, Hudson Institute of Medical Research, Clayton 3168, Australia.ORCID 0000-0003-4496-2263
Kirsty L WilsonSchool of Health and Biomedical Sciences, RMIT University, Bundoora 3083, Australia.
Maree BilandzicCentre for Cancer Research, Hudson Institute of Medical Research, Clayton 3168, Australia.ORCID 0000-0002-6319-1153
Mark D WrightDepartment of Immunology and Pathology, Monash University, Clayton 3800, Australia.ORCID 0000-0002-2177-5214
Mark D GorrellCentenary Institute, Faculty of Medicine and Health, University of Sydney, Camperdown 2006, Australia.ORCID 0000-0002-0528-2604
Martin K OehlerDepartment of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide 5000, Australia.
Magdalena PlebanskiSchool of Health and Biomedical Sciences, RMIT University, Bundoora 3083, Australia.ORCID 0000-0001-6889-3667
Andrew N StephensCentre for Cancer Research, Hudson Institute of Medical Research, Clayton 3168, Australia.ORCID 0000-0003-2420-8458
Hudson Institute of Medical Research · AURMIT University · AUMonash University · AURoyal Adelaide Hospital · AUThe University of Sydney · AU

Funding

National Health and Medical Research Council 1099375
6 · The paper itself

Abstract

Immunity plays a key role in epithelial ovarian cancer (EOC) progression with a well-documented correlation between patient survival and high intratumoral CD8+ to T regulatory cell (Treg) ratios. We previously identified dysregulated DPP4 activity in EOCs as a potentially immune-disruptive influence contributing to a reduction in CXCR3-mediated T-cell infiltration in solid tumours. We therefore hypothesized that inhibition of DPP4 activity by sitagliptin, an FDA-approved inhibitor, would improve T-cell infiltration and function in a syngeneic ID8 mouse model of EOC. Daily oral sitagliptin at 50 mg/kg was provided to mice with established primary EOCs. Sitagliptin treatment decreased metastatic tumour burden and significantly increased overall survival and was associated with significant changes to the immune landscape. Sitagliptin increased overall CXCR3-mediated CD8+ T-cell trafficking to the tumour and enhanced the activation and proliferation of CD8+ T-cells in tumour tissue and the peritoneal cavity. Substantial reductions in suppressive cytokines, including CCL2, CCL17, CCL22 and IL-10, were also noted and were associated with reduced CD4+ CD25+ Foxp3+ Treg recruitment in the tumour. Combination therapy with paclitaxel, however, typical of standard-of-care for patients in palliative care, abolished CXCR3-specific T-cell recruitment stimulated by sitagliptin. Our data suggest that sitagliptin may be suitable as an adjunct therapy for patients between chemotherapy cycles as a novel approach to enhance immunity, optimise T-cell-mediated function and improve overall survival.

Indexed as

DPP4ID8immuneovarian cancersitagliptinsyngeneicT-cell

Identifiers

PMID33513866
PMCPMC7865851
OpenAlexW3121271462

What Socratic holds

Textmetadata
LicenceCC BY
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.