Evidence map›Paper›PMID 34035069›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021

Single-Cell Characterization of the Immune Microenvironment of Melanoma Brain and Leptomeningeal Metastases.

Inna Smalley, Zhihua Chen, Manali Phadke, Jiannong Li, Xiaoqing Yu, Clayton Wyatt, Brittany Evernden, Jane L Messina, Amod Sarnaik, Vernon K Sondak and 10 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.

0numbers the graph read from it
0cells of the map it votes in
119citing papers in PubMed
9.9field-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.

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

119 citing papers in PubMed, 155 citations in OpenAlex.

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  8. Spatiotemporal dynamics of adoptively transferred stem-like CD8bioRxiv : the preprint server for biology · 2026
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59 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

20 authors at 1 institution in 1 country.

Inna Smalley *The Department of Tumor Biology, The Moffitt Cancer Center and Research Institute, Tampa, Florida. keiran.smalley@moffitt.org inna.smalley@moffitt.org ann.chen@moffitt.org.ORCID 0000-0002-6796-9145
Zhihua Chen *Department of Bioinformatics and Biostatistics, The Moffitt Cancer Center and Research Institute, Tampa, Florida.
Manali PhadkeThe Department of Tumor Biology, The Moffitt Cancer Center and Research Institute, Tampa, Florida.
Jiannong LiDepartment of Bioinformatics and Biostatistics, The Moffitt Cancer Center and Research Institute, Tampa, Florida.
Xiaoqing YuDepartment of Bioinformatics and Biostatistics, The Moffitt Cancer Center and Research Institute, Tampa, Florida.
Clayton WyattThe Department of Tumor Biology, The Moffitt Cancer Center and Research Institute, Tampa, Florida.ORCID 0000-0003-2703-5310
Brittany EverndenDepartment of Neurooncology, The Moffitt Cancer Center and Research Institute, Tampa, Florida.
Jane L MessinaDepartment of Cutaneous Oncology, The Moffitt Cancer Center and Research Institute, Tampa, Florida.ORCID 0000-0002-0332-0224
Amod SarnaikDepartment of Cutaneous Oncology, The Moffitt Cancer Center and Research Institute, Tampa, Florida.
Vernon K SondakDepartment of Cutaneous Oncology, The Moffitt Cancer Center and Research Institute, Tampa, Florida.
Chaomei ZhangMolecular Genomics Core, The Moffitt Cancer Center and Research Institute, Tampa, Florida.
Vincent LawDepartment of Neurooncology, The Moffitt Cancer Center and Research Institute, Tampa, Florida.
Nam TranDepartment of Neurooncology, The Moffitt Cancer Center and Research Institute, Tampa, Florida.ORCID 0000-0002-9488-3988
Arnold EtameDepartment of Neurooncology, The Moffitt Cancer Center and Research Institute, Tampa, Florida.ORCID 0000-0002-9656-4702
Robert J B MacaulayDepartment of Neurooncology, The Moffitt Cancer Center and Research Institute, Tampa, Florida.ORCID 0000-0003-1115-3654
Zeynep ErogluDepartment of Cutaneous Oncology, The Moffitt Cancer Center and Research Institute, Tampa, Florida.
Peter A ForsythDepartment of Neurooncology, The Moffitt Cancer Center and Research Institute, Tampa, Florida.ORCID 0000-0002-3756-8594
Paulo C RodriguezDepartment of Immunology, The Moffitt Cancer Center and Research Institute, Tampa, Florida.
Y Ann ChenDepartment of Bioinformatics and Biostatistics, The Moffitt Cancer Center and Research Institute, Tampa, Florida. keiran.smalley@moffitt.org inna.smalley@moffitt.org ann.chen@moffitt.org.
Keiran S M SmalleyThe Department of Tumor Biology, The Moffitt Cancer Center and Research Institute, Tampa, Florida. keiran.smalley@moffitt.org inna.smalley@moffitt.org ann.chen@moffitt.org.
Moffitt Cancer Center · US

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5M
Project 4P01CA250984 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI RODRIGUEZ, PAULO CESAR · 2021 to 2025
$10.1M
Tissue, Pathology and BioinformaticsP50CA168536 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI MULE, JAMES J. · 2013 to 2017
$8.5M
Functional reprogramming of tumor-MDSC through antibody-based therapies targeting Notch ligandsR01CA233512 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI RODRIGUEZ, PAULO CESAR · 2019 to 2023
$2.0M
Stress Pathways in Tumors Drive Global MDSC Activity and Survival through ChopR01CA184185 · NCI · LSU HEALTH SCIENCES CENTER · PI RODRIGUEZ, PAULO CESAR · 2015 to 2019
$1.8M
Defining the Role of Metabolic Heterogeneity in Melanoma Dissemination and Therapy EscapeR00CA226679 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI SMALLEY, INNA · 2020 to 2022
$747k
Modeling and Targeting Adaptive Signaling Responses in Single NRAS Mutant Melanoma CellsR21CA198550 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI SMALLEY, KEIRAN · 2015 to 2016
$422k
Using Single Cell Analysis to identify therapeutic vulnerabilities in leptomeningeal melanoma metastasesR21CA216756 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI FORSYTH, PETER ALEXANDER, SMALLEY, KEIRAN · 2017 to 2018
$412k
Defining the role of metabolic heterogeneity in melanoma dissemination and therapy escapeK99CA226679 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI SMALLEY, INNA · 2018 to 2019
$197k
NCI NIH HHS K99 CA226679NCI NIH HHS P01 CA250984NCI NIH HHS P30 CA076292NCI NIH HHS P50 CA168536NCI NIH HHS R00 CA226679NCI NIH HHS R01 CA184185NCI NIH HHS R01 CA233512NCI NIH HHS R21 CA198550NCI NIH HHS R21 CA216756
6 · The paper itself

Abstract

purposeMelanoma brain metastases (MBM) and leptomeningeal melanoma metastases (LMM) are two different manifestations of melanoma CNS metastasis. Here, we used single-cell RNA sequencing (scRNA-seq) to define the immune landscape of MBM, LMM, and melanoma skin metastases. EXPERIMENTAL

designscRNA-seq was undertaken on 43 patient specimens, including 8 skin metastases, 14 MBM, and 19 serial LMM specimens. Detailed cell type curation was performed, the immune landscapes were mapped, and key results were validated by IHC and flow cytometry. Association analyses were undertaken to identify immune cell subsets correlated with overall survival.

resultsThe LMM microenvironment was characterized by an immune-suppressed T-cell landscape distinct from that of brain and skin metastases. An LMM patient with long-term survival demonstrated an immune repertoire distinct from that of poor survivors and more similar to normal cerebrospinal fluid (CSF). Upon response to PD-1 therapy, this extreme responder showed increased levels of T cells and dendritic cells in their CSF, whereas poor survivors showed little improvement in their T-cell responses. In MBM patients, therapy led to increased immune infiltrate, with similar T-cell transcriptional diversity noted between skin metastases and MBM. A correlation analysis across the entire immune landscape identified the presence of a rare population of dendritic cells (DC3) that was associated with increased overall survival and positively regulated the immune environment through modulation of activated T cells and MHC expression.

conclusionsOur study provides the first atlas of two distinct sites of melanoma CNS metastases and defines the immune cell landscape that underlies the biology of this devastating disease.

Indexed as

Brain NeoplasmsHumansMelanomaMeningeal NeoplasmsSkin NeoplasmsTumor Microenvironment

Identifiers

PMID34035069
PMCPMC8282775
OpenAlexW3165815938

What OpenQuestion holds

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Registered trials

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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.