Evidence map›Paper›PMID 27471641›Full record

ArticleOncoimmunology2016

Antitumor vaccination of prostate cancer patients elicits PD-1/PD-L1 regulated antigen-specific immune responses.

Brian T Rekoske, Brian M Olson, Douglas G McNeel

Abstract read
In one paragraph

Article in Oncoimmunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 5 pooled it
–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

40 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Trial
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Toll-like receptor agonists as cancer vaccine adjuvants.Human vaccines & immunotherapeutics · 2024
    Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Review
  18. The roles of PD-1/PD-L1 in the prognosis and immunotherapy of prostate cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Review
  19. Mechanisms of PD-L1 Regulation in Malignant and Virus-Infected Cells.International journal of molecular sciences · 2021
    Review
  20. Review
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

3 authors.

Brian T RekoskeDepartment of Medicine, University of Wisconsin-Madison , Madison, WI, USA.
Brian M OlsonCarbone Cancer Center, University of Wisconsin-Madison , Madison, WI, USA.
Douglas G McNeelDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA; Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.

Funding

Institutional Clinical and Translational Science AwardUL1TR000427 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2012 to 2016
$32.2M
GRADUATE TRAINING IN MOLECULAR BIOSCIENCEST32GM007215 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI HULL, CHRISTINA M · 1985 to 2018
$22.5M
NCATS NIH HHS UL1 TR000427NIGMS NIH HHS T32 GM007215
6 · The paper itself

Abstract

We have previously reported that tumor antigen-specific DNA vaccination in mice led to an increase in IFNγ-secreting T cells and an increase in tumor expression of PD-L1. Further, we demonstrated that increasing the encoded antigen's MHC-binding affinity led to increased PD-1 expression on antigen-specific CD8(+) T cells. Together these phenomena provided resistance to antitumor immunization that was abrogated with PD-1/PD-L1 blockade. We consequently sought to determine whether similar regulation occurred in human patients following antitumor immunization. Using clinical samples from prostate cancer patients who were previously immunized with a DNA vaccine, we analyzed changes in checkpoint receptor expression on antigen-specific CD8(+) T cells, the effect of PD-1 blockade on elicited immune responses, and for changes in checkpoint ligand expression on patients' circulating tumor cells (CTCs). We observed no significant changes in T-cell expression of PD-1 or other checkpoint receptors, but antigen-specific immune responses were detected and/or augmented with PD-1 blockade as detected by IFNγ and granzyme B secretion or trans vivo DTH testing. Moreover, PD-L1 expression was increased on CTCs following vaccination, and this PD-L1 upregulation was associated with the development of sustained T-cell immunity and longer progression-free survival. Finally, similar results were observed with patients treated with sipuleucel-T, another vaccine targeting the same prostate antigen. These findings provide in-human rationale for combining anticancer vaccines with PD-1 blocking antibodies, particularly for the treatment of prostate cancer, a disease for which vaccines have demonstrated benefit and yet PD-1 inhibitors have shown little clinical benefit to date as monotherapies.

Indexed as

DNA vaccinePD-1PD-L1prostate cancerprostatic acid phosphatase (PAP)

Identifiers

PMID27471641
PMCPMC4938302

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.