Evidence map›Paper›PMID 26787823›Full record

ArticleCancer immunology research2016

PD-1 Blockade Expands Intratumoral Memory T Cells.

Antoni Ribas, Daniel Sanghoon Shin, Jesse Zaretsky, Juliet Frederiksen, Andrew Cornish, Earl Avramis, Elizabeth Seja, Christine Kivork, Janet Siebert, Paula Kaplan-Lefko and 7 more

Open access · bronzeAbstract readClinical Trial, Phase I
In one paragraph

Article in Cancer immunology research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 243 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
243citing papers in PubMed, 6 pooled it
22.4field-weighted citation impact, top 1% 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

243 citing papers in PubMed, 6 syntheses or guidelines pooled it, 401 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Guideline
  5. Pooled it
  6. Pooled it
  7. Trial
  8. Trial
  9. Combined Targeting of PD-1 and TIM-3 in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer: AMBER Part 2B.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Trial
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001.Annals of oncology : official journal of the European Society for Medical Oncology · 2019
    Trial
  15. Trial
  16. Review
  17. Article
  18. Adaptive resistance in cancer immunotherapy.Cellular & molecular immunology · 2026
    Review
  19. Article
  20. Article

183 more citing papers are in PubMed but not listed here.

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

17 authors at 1 institution.

Antoni RibasDivision of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California. Division of Surgical-Oncology, Department of Surgery, University of California Los Angeles, Los Angeles, California. Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California. Jonsson Comprehensive Cancer Center, Los Angeles, California. bcomin@mednet.ucla.edu aribas@mednet.ucla.edu.
Daniel Sanghoon ShinDivision of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California.
Jesse ZaretskyDivision of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California.
Juliet FrederiksenCenter for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
Andrew CornishDepartments of Biological Sciences and Systems Biology, Columbia University, New York, New York.
Earl AvramisDivision of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California.
Elizabeth SejaDivision of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California.
Christine KivorkDivision of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California.
Janet SiebertCytoAnalysis, Denver, Colorado.
Paula Kaplan-LefkoDivision of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California.
Xiaoyan WangDepartment of General Internal Medicine and Healthy Services Research, University of California Los Angeles, Los Angeles, California.
Bartosz ChmielowskiDivision of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California.
John A GlaspyDivision of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California.
Paul C TumehDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California. Jonsson Comprehensive Cancer Center, Los Angeles, California. Department of Medicine, Division of Dermatology. University of California Los Angeles, Los Angeles, California.
Thinle ChodonCenter for Immunotherapy, Roswell Park Cancer Institute, Buffalo, New York.
Dana Pe'erDepartments of Biological Sciences and Systems Biology, Columbia University, New York, New York.
Begoña Comin-AnduixDivision of Surgical-Oncology, Department of Surgery, University of California Los Angeles, Los Angeles, California. Jonsson Comprehensive Cancer Center, Los Angeles, California. bcomin@mednet.ucla.edu aribas@mednet.ucla.edu.
UCLA Jonsson Comprehensive Cancer Center

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CUMBERLAND, WILLIAM GLEN · 1991 to 2018
$39.9M
UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
Next Generation Cancer Immunotherapies to Defeat MelanomaR35CA197633 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANTONI RIBAS · 2015 to 2026
$10.4M
UCLA Tumor Immunology Training ProgramT32CA009120 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Steven M. Dubinett, MICHAEL A TEITELL · 1985 to 2026
$10.3M
TARGETED COMBINATORIAL TREATMENT OF BRAF MELANOMASP01CA168585 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RIBAS, ANTONI · 2013 to 2017
$8.4M
ACADEMIC TRAINING IN MEDICAL ONCOLOGYT32CA009297 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RIBAS, ANTONI · 1985 to 2013
$3.3M
Dermatology Scientist Training ProgramT32AR058921 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MODLIN, ROBERT L · 2010 to 2014
$877k
NCI NIH HHS 5T32CA009120-39NCI NIH HHS 5T32CA009297-30NCI NIH HHS CA16042NCI NIH HHS P01 CA168585NCI NIH HHS P30 CA016042NCI NIH HHS R35 CA197633NCI NIH HHS T32 CA009120NCI NIH HHS T32 CA009297NIAID NIH HHS AI 28697NIAID NIH HHS P30 AI028697NIAMS NIH HHS 5T32AR058921-05NIAMS NIH HHS T32 AR058921NIGMS NIH HHS T32 GM008042
6 · The paper itself

Abstract

Tumor responses to programmed cell death protein 1 (PD-1) blockade therapy are mediated by T cells, which we characterized in 102 tumor biopsies obtained from 53 patients treated with pembrolizumab, an antibody to PD-1. Biopsies were dissociated, and single-cell infiltrates were analyzed by multicolor flow cytometry using two computational approaches to resolve the leukocyte phenotypes at the single-cell level. There was a statistically significant increase in the frequency of T cells in patients who responded to therapy. The frequency of intratumoral B cells and monocytic myeloid-derived suppressor cells significantly increased in patients' biopsies taken on treatment. The percentage of cells with a regulatory T-cell phenotype, monocytes, and natural killer cells did not change while on PD-1 blockade therapy. CD8(+) memory T cells were the most prominent phenotype that expanded intratumorally on therapy. However, the frequency of CD4(+) effector memory T cells significantly decreased on treatment, whereas CD4(+) effector T cells significantly increased in nonresponding tumors on therapy. In peripheral blood, an unusual population of blood cells expressing CD56 was detected in two patients with regressing melanoma. In conclusion, PD-1 blockade increases the frequency of T cells, B cells, and myeloid-derived suppressor cells in tumors, with the CD8(+) effector memory T-cell subset being the major T-cell phenotype expanded in patients with a response to therapy.

Indexed as

AgedAntibodies, Monoclonal, HumanizedAntineoplastic AgentsFemaleHumansMaleMelanomaMiddle AgedProgrammed Cell Death 1 ReceptorSkin NeoplasmsT-Lymphocyte SubsetsTreatment OutcomeAntibodies, Monoclonal, HumanizedAntineoplastic AgentsPDCD1 protein, humanpembrolizumabProgrammed Cell Death 1 Receptor

Identifiers

PMID26787823
PMCPMC4775381
OpenAlexW2281666530

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.