Evidence map›Paper›PMID 25968455›Full record

ArticleCancer immunology research2015

Preexisting Levels of CD4 T Cells Expressing PD-1 Are Related to Overall Survival in Prostate Cancer Patients Treated with Ipilimumab.

Serena S Kwek, Jera Lewis, Li Zhang, Vivian Weinberg, Samantha K Greaney, Andrea L Harzstark, Amy M Lin, Charles J Ryan, Eric J Small, Lawrence Fong

Open access · bronzeAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer immunology research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 4 pooled it
3.7field-weighted citation impact, top 5% 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

42 citing papers in PubMed, 4 syntheses or guidelines pooled it, 60 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Trial
  7. Trial
  8. CTLA-4: a promising immunosuppressive immune checkpoint in prostate cancer therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  9. Review
  10. CD4Trends in cancer · 2024
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Cytotoxic CD4Immunity · 2021
    Review
  20. 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

10 authors at 2 institutions in 1 country.

Serena S KwekDivision of Hematology/Oncology, University of California, San Francisco, California.
Jera LewisDivision of Hematology/Oncology, University of California, San Francisco, California.
Li ZhangDivision of Hematology/Oncology, University of California, San Francisco, California. UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
Vivian WeinbergUCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
Samantha K GreaneyDivision of Hematology/Oncology, University of California, San Francisco, California.
Andrea L HarzstarkDivision of Hematology/Oncology, University of California, San Francisco, California.
Amy M LinDivision of Hematology/Oncology, University of California, San Francisco, California.
Charles J RyanDivision of Hematology/Oncology, University of California, San Francisco, California. UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
Eric J SmallDivision of Hematology/Oncology, University of California, San Francisco, California. UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
Lawrence FongDivision of Hematology/Oncology, University of California, San Francisco, California. UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California. lfong@medicine.ucsf.edu.
University of California, San Francisco · USUCSF Helen Diller Family Comprehensive Cancer Center · US

Funding

UCSF CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR024131 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOHNSTON, S. CLAIBORNE · 2006 to 2011
$111.2M
Prostatitis and Prostate Cancer DevelopmentR01CA163012 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FONG, LAWRENCE · 2012 to 2016
$2.0M
Prostate Cancer ImmunotherapyR01CA136753 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FONG, LAWRENCE · 2009 to 2013
$1.6M
NCI NIH HHS R01 CA136753NCI NIH HHS R01-CA136753NCI NIH HHS R01 CA163012NCI NIH HHS R01-CA163012NCRR NIH HHS UL1 RR024131
6 · The paper itself

Abstract

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) blockade can induce tumor regression and improved survival in cancer patients. This treatment can enhance adaptive immune responses without an exogenous vaccine, but the immunologic biomarkers associated with improved clinical outcome in cancer patients are not fully established. A phase Ib trial in patients with metastatic, castration-resistant prostate cancer was performed combining ipilimumab with sargramostim (GM-CSF). In addition to evaluating ipilimumab dose, patients were followed clinically for response and overall survival, and for immunomodulation of circulating T cells. PSA declines of ≥50% and radiographic responses were observed at doses of ≥3 mg/kg/dose. Timing of clinical responses could be either immediate or delayed. Durable responses were also observed off treatment. A subset of patients experienced long-term survival with or without objective clinical responses. The relationship between T-cell phenotype in peripheral blood and overall survival was examined retrospectively. We found that the treatment induced an increase in the levels of CD4(+) effector T (Teff) cells, regulatory T cells, PD-1(+) CD4 Teff cells, and PD-1(+) CD8 T cells. However, these increased levels were not associated with overall survival. Instead, low pretreatment baseline levels of PD-1(+) CD4 Teff cells were found to correlate with longer overall survival. Furthermore, baseline levels of PD-1(+) CD4 Teff cells from patients with shorter overall survival were higher than from cancer-free male control subjects. These results suggest that preexisting expression of immunologic checkpoint marker PD-1 on CD4 Teff cells may help identify patients that may benefit from ipilimumab treatment.

Indexed as

AgedAged, 80 and overAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCD4-Positive T-LymphocytesCTLA-4 AntigenDose-Response Relationship, DrugFollow-Up StudiesGranulocyte-Macrophage Colony-Stimulating FactorHumansIpilimumabKallikreinsLymphocyte CountMaleMiddle AgedAntibodies, MonoclonalBiomarkers, TumorCTLA-4 AntigenGranulocyte-Macrophage Colony-Stimulating FactorIpilimumabKallikreinsKLK3 protein, humanNeoplasm ProteinsPDCD1 protein, humanProgrammed Cell Death 1 ReceptorProstate-Specific AntigenRecombinant Proteinssargramostim

Identifiers

PMID25968455
PMCPMC4561203
OpenAlexW2133929618

What OpenQuestion holds

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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 OpenQuestion graph.