Evidence map›Paper›PMID 24871131›Full record

ArticleScience translational medicine2014

Improved survival with T cell clonotype stability after anti-CTLA-4 treatment in cancer patients.

Edward Cha, Mark Klinger, Yafei Hou, Craig Cummings, Antoni Ribas, Malek Faham, Lawrence Fong

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 251 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
251citing papers in PubMed, 4 pooled it
17.4field-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

251 citing papers in PubMed, 4 syntheses or guidelines pooled it, 379 citations in OpenAlex.

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191 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

7 authors at 2 institutions in 1 country.

Edward ChaUniversity of California, San Francisco, San Francisco, CA 94143, USA.
Mark KlingerSequenta, South San Francisco, CA 94080, USA.
Yafei HouUniversity of California, San Francisco, San Francisco, CA 94143, USA.
Craig CummingsSequenta, South San Francisco, CA 94080, USA.
Antoni RibasUniversity of California, Los Angeles, Los Angeles, CA 90095, USA.
Malek FahamSequenta, South San Francisco, CA 94080, USA.
Lawrence FongUniversity of California, San Francisco, San Francisco, CA 94143, USA. lfong@medicine.ucsf.edu.
University of California, San Francisco · USUniversity of California, Los Angeles · US

Funding

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 1R01 CA136753NCI NIH HHS 1R01 CA163012NCI NIH HHS R01 CA136753NCI NIH HHS R01 CA163012
6 · The paper itself

Abstract

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) blockade can promote antitumor T cell immunity and clinical responses. The mechanism by which anti-CTLA-4 antibodies induces antitumor responses is controversial. To determine the effects of CTLA-4 blockade on the T cell repertoire, we used next-generation deep sequencing to measure the frequency of individual rearranged T cell receptor β (TCRβ) genes, thereby characterizing the diversity of rearrangements, known as T cell clonotypes. CTLA-4 blockade in patients with metastatic castration-resistant prostate cancer and metastatic melanoma resulted in both expansion and loss of T cell clonotypes, consistent with a global turnover of the T cell repertoire. Overall, this treatment increased TCR diversity as reflected in the number of unique TCR clonotypes. The repertoire of clonotypes continued to evolve over subsequent months of treatment. Whereas the number of clonotypes that increased with treatment was not associated with clinical outcome, improved overall survival was associated with maintenance of high-frequency clones at baseline. In contrast, the highest-frequency clonotypes fell with treatment in patients with short overall survival. Stably maintained clonotypes included T cells having high-avidity TCR such as virus-reactive T cells. Together, these results suggest that CTLA-4 blockade induces T cell repertoire evolution and diversification. Moreover, improved clinical outcomes are associated with less clonotype loss, consistent with the maintenance of high-frequency TCR clonotypes during treatment. These clones may represent the presence of preexisting high-avidity T cells that may be relevant in the antitumor response.

Indexed as

Survival AnalysisAntibodies, MonoclonalCTLA-4 AntigenHumansNeoplasmsAntibodies, MonoclonalCTLA-4 Antigen

Identifiers

PMID24871131
PMCPMC4558099
OpenAlexW1998927848

What OpenQuestion holds

Textmetadata
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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.