Evidence map›Paper›PMID 27467953›Full record

ArticleOncoimmunology2016

The ratio of CD8 to Treg tumor-infiltrating lymphocytes is associated with response to cisplatin-based neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder.

Alexander S Baras, Charles Drake, Jen-Jane Liu, Nilay Gandhi, Max Kates, Mohamed O Hoque, Alan Meeker, Noah Hahn, Janis M Taube, Mark P Schoenberg and 2 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
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. It is linked to trial NCT04872036 (Investigation of Prognostic Biomarkers in Patients With Urothelial Carcinoma Treated With Platinum Regimens), which is not on this map. Cited by 104 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed, 1 pooled it
17.9field-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.

NCT04872036 completednot on this map

Investigation of Prognostic Biomarkers in Patients With Urothelial Carcinoma Treated With Platinum Regimens

TypeobservationalSponsorHellenic Cooperative Oncology GroupRan2000 to 2017Enrolled66ConditionsBladder Cancer
3 · Its place in the literature

Who cites it

104 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.

  1. Pooled it
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  4. PD1-IL2v expands and induces effector CD8Journal of experimental & clinical cancer research : CR · 2026
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44 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

12 authors at 5 institutions in 1 country.

Alexander S BarasDepartment of Pathology, Johns Hopkins, Baltimore, MD, USA; Department of Urology, Johns Hopkins, Baltimore, MD, USA.
Charles DrakeDepartment of Urology, Johns Hopkins, Baltimore, MD, USA; Department of Oncology, Johns Hopkins, Baltimore, MD, USA.
Jen-Jane LiuDepartment of Urology, Johns Hopkins , Baltimore, MD, USA.
Nilay GandhiDepartment of Urology, Johns Hopkins , Baltimore, MD, USA.
Max KatesDepartment of Urology, Johns Hopkins , Baltimore, MD, USA.
Mohamed O HoqueDepartment of Oncology, Johns Hopkins , Baltimore, MD, USA.
Alan MeekerDepartment of Pathology, Johns Hopkins , Baltimore, MD, USA.
Noah HahnDepartment of Urology, Johns Hopkins, Baltimore, MD, USA; Department of Oncology, Johns Hopkins, Baltimore, MD, USA.
Janis M TaubeDepartment of Pathology, Johns Hopkins, Baltimore, MD, USA; Department of Dermatology, Johns Hopkins; Baltimore, MD, USA.
Mark P SchoenbergDepartment of Urology, Montefiore Medical Center , Bronx, NY, USA.
George NettoDepartment of Pathology, Johns Hopkins, Baltimore, MD, USA; Department of Urology, Johns Hopkins, Baltimore, MD, USA; Department of Oncology, Johns Hopkins, Baltimore, MD, USA.
Trinity J BivalacquaDepartment of Urology, Johns Hopkins, Baltimore, MD, USA; Department of Oncology, Johns Hopkins, Baltimore, MD, USA.
Johns Hopkins University · USJohns Hopkins Hospital · USJohns Hopkins Medicine · USMontefiore Medical Center · USUniversity of Baltimore · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionRandomized controlled trials of platinum-based neoadjuvant chemotherapy (NAC) for bladder cancer have shown that patients who achieve a pathologic response to NAC exhibit 5 y survival rates of approximately 80-90% while NAC resistant (NR) cases exhibit 5 y survival rates of approximately 30-40%. These findings highlight the need to predict who will benefit from conventional NAC and the need for plausible alternatives.

methodsThe pre-treatment biopsy tissues from a cohort of 41 patients with muscle invasive bladder who were treated with NAC were incorporated in tissue microarray and immunohistochemistry for PD-L1, CD8, and FOXP3 was performed. Percentage of PD-L1 positive tumor cells was measured. Tumor-infiltrating lymphocytes (TIL) densities, along with CD8 and Treg-specific TILs, were measured.

resultsTIL density was strongly correlated with tumor PD-L1 expression, consistent with the mechanism of adaptive immune resistance in bladder cancer. Tumor cell PD-L1 expression was not a significant predictor of response. Neither was the CD8 nor Treg TIL density associated with response. Intriguingly though, the ratio of CD8 to Treg TIL densities was strongly associated with response (p = 0.0003), supporting the hypothesis that the immune system plays a role in the response of bladder cancer to chemotherapy. DISCUSSION: To our knowledge, this is the first report in bladder cancer showing that the CD8 to Treg TIL density in the pre-treatment tissues is predictive for conventional NAC response. These findings warrant further investigations to both better characterize this association in larger cohorts and begin to elucidate the underlying mechanism(s) of this phenomenon.

Indexed as

Biomarkers; bladder cancer; chemotherapy; immunology; neoadjuvant

Identifiers

PMID27467953
PMCPMC4910705
OpenAlexW2418644771

What OpenQuestion holds

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Registered trials

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.