Evidence map›Paper›PMID 29320474›Full record

ArticleNature2018

High response rate to PD-1 blockade in desmoplastic melanomas.

Zeynep Eroglu, Jesse M Zaretsky, Siwen Hu-Lieskovan, Dae Won Kim, Alain Algazi, Douglas B Johnson, Elizabeth Liniker, Ben Kong, Rodrigo Munhoz, Suthee Rapisuwon and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 195 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
195citing 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

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

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  9. The Role of Anti-PD-1/PD-L1 in the Treatment of Skin Cancer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2020
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135 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Zeynep ErogluUniversity of California Los Angeles, Los Angeles, California, USA.
Jesse M ZaretskyUniversity of California Los Angeles, Los Angeles, California, USA.
Siwen Hu-LieskovanUniversity of California Los Angeles, Los Angeles, California, USA.
Dae Won KimMoffitt Cancer Center and University of South Florida, Tampa, Florida, USA.
Alain AlgaziUniversity of California San Francisco, San Francisco, California, USA.
Douglas B JohnsonVanderbilt Ingram Cancer Center, Nashville, Tennessee, USA.
Elizabeth LinikerMelanoma Institute Australia, Sydney, New South Wales, Australia.
Ben KongWestmead Hospital, Sydney, New South Wales, Australia.
Rodrigo MunhozMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Suthee RapisuwonGeorgetown Lombardi Cancer Center, Washington DC, USA.
Pier Federico GherardiniParker Institute for Cancer Immunotherapy, San Francisco, California, USA.
Bartosz ChmielowskiUniversity of California Los Angeles, Los Angeles, California, USA.
Xiaoyan WangUniversity of California Los Angeles, Los Angeles, California, USA.
I Peter ShintakuUniversity of California Los Angeles, Los Angeles, California, USA.
Cody WeiUniversity of California Los Angeles, Los Angeles, California, USA.
Jeffrey A SosmanVanderbilt Ingram Cancer Center, Nashville, Tennessee, USA.
Richard W JosephMayo Clinic, Jacksonville, Florida, USA.
Michael A PostowMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Matteo S CarlinoMelanoma Institute Australia, Sydney, New South Wales, Australia.
Wen-Jen HwuThe University of Texas-MD Anderson Cancer Center, Houston, Texas, USA.
Richard A ScolyerMelanoma Institute Australia, Sydney, New South Wales, Australia.
Jane MessinaMoffitt Cancer Center and University of South Florida, Tampa, Florida, USA.
Alistair J CochranUniversity of California Los Angeles, Los Angeles, California, USA.
Georgina V LongMelanoma Institute Australia, Sydney, New South Wales, Australia.
Antoni RibasUniversity of California Los Angeles, Los Angeles, California, USA.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5M
UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
Vanderbilt Clinical Oncology Research Career Development ProgramK12CA090625 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Debra L. Friedman, Paula Jill Hurley · 2001 to 2026
$16.9M
Next Generation Cancer Immunotherapies to Defeat MelanomaR35CA197633 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANTONI RIBAS · 2015 to 2026
$10.4M
Tissue, Pathology and BioinformaticsP50CA168536 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI MULE, JAMES J. · 2013 to 2017
$8.5M
TARGETED COMBINATORIAL TREATMENT OF BRAF MELANOMASP01CA168585 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LO, ROGER S · 2013 to 2017
$8.4M
NCI NIH HHS K12 CA090625NCI NIH HHS P01 CA168585NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA076292NCI NIH HHS P50 CA168536NCI NIH HHS R35 CA197633NIGMS NIH HHS T32 GM008042
6 · The paper itself

Abstract

Desmoplastic melanoma is a rare subtype of melanoma characterized by dense fibrous stroma, resistance to chemotherapy and a lack of actionable driver mutations, and is highly associated with ultraviolet light-induced DNA damage. We analysed sixty patients with advanced desmoplastic melanoma who had been treated with antibodies to block programmed cell death 1 (PD-1) or PD-1 ligand (PD-L1). Objective tumour responses were observed in forty-two of the sixty patients (70%; 95% confidence interval 57-81%), including nineteen patients (32%) with a complete response. Whole-exome sequencing revealed a high mutational load and frequent NF1 mutations (fourteen out of seventeen cases) in these tumours. Immunohistochemistry analysis from nineteen desmoplastic melanomas and thirteen non-desmoplastic melanomas revealed a higher percentage of PD-L1-positive cells in the tumour parenchyma in desmoplastic melanomas (P = 0.04); these cells were highly associated with increased CD8 density and PD-L1 expression in the tumour invasive margin. Therefore, patients with advanced desmoplastic melanoma derive substantial clinical benefit from PD-1 or PD-L1 immune checkpoint blockade therapy, even though desmoplastic melanoma is defined by its dense desmoplastic fibrous stroma. The benefit is likely to result from the high mutational burden and a frequent pre-existing adaptive immune response limited by PD-L1 expression.

Indexed as

ImmunotherapyB7-H1 AntigenBiopsyCD8-Positive T-LymphocytesCell Cycle CheckpointsHumansMelanomaMutationNeurofibromin 1Programmed Cell Death 1 ReceptorRetrospective StudiesB7-H1 AntigenCD274 protein, humanNeurofibromin 1PDCD1 protein, humanProgrammed Cell Death 1 Receptor

Identifiers

PMID29320474
PMCPMC5773412

What OpenQuestion holds

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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.