Evidence map›Paper›PMID 39554029›Full record

ArticlebioRxiv : the preprint server for biology2024

Stratified analysis identifies HIF-2

Amy Y Huang, Kelly P Burke, Ryan Porter, Lynn Meiger, Peter Fatouros, Jiekun Yang, Emily Robitschek, Natalie Vokes, Cora Ricker, Valeria Rosado and 16 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

26 authors.

Amy Y HuangDana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0002-6646-6503
Kelly P BurkeDana-Farber Cancer Institute, Boston, MA, USA.
Ryan PorterDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Lynn MeigerDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Peter FatourosDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Jiekun YangBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Emily RobitschekDana-Farber Cancer Institute, Boston, MA, USA.
Natalie VokesUniversity of Texas MD Anderson Cancer Center, Houston, USA.
Cora RickerDana-Farber Cancer Institute, Boston, MA, USA.
Valeria RosadoDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Giuseppe TarantinoDana-Farber Cancer Institute, Boston, MA, USA.
Jiajia ChenDana-Farber Cancer Institute, Boston, MA, USA.
Tyler J ApratiDana-Farber Cancer Institute, Boston, MA, USA.
Marc C GlettigDana-Farber Cancer Institute, Boston, MA, USA.
Yiwen HeDana-Farber Cancer Institute, Boston, MA, USA.
Cassia WangMassachusetts Institute of Technology, Cambridge, USA.
Doris FuMassachusetts Institute of Technology, Cambridge, USA.
Li-Lun HoBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Kyriakitsa GalaniBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Gordon J FreemanDana-Farber Cancer Institute, Boston, MA, USA.
Elizabeth I BuchbinderDana-Farber Cancer Institute, Boston, MA, USA.
F Stephen HodiDana-Farber Cancer Institute, Boston, MA, USA.
Manolis KellisBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Genevieve M BolandBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
Arlene H SharpeBroad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
David LiuDana-Farber Cancer Institute, Boston, MA, USA.

Funding

Treating the P13-Kinase/AKTP50CA101942 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI David McDermott · 2003 to 2026
$53.4M
Physician Scientist Training in Cancer ResearchT32CA009172 · NCI · DANA-FARBER CANCER INSTITUTE · PI Jennifer R Brown, James A. DeCaprio · 1985 to 2026
$17.1M
Dissecting Therapeutic Resistance and Progression in Metastatic Melanoma Through Clinical Computational OncologyK08CA234458 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI LIU, DAVID · 2018 to 2022
$1.2M
NCI NIH HHS K08 CA234458NCI NIH HHS P50 CA101942NCI NIH HHS T32 CA009172
6 · The paper itself

Abstract

While immune-checkpoint blockade (ICB) has revolutionized treatment of metastatic melanoma over the last decade, the identification of broadly applicable robust biomarkers has been challenging, driven in large part by the heterogeneity of ICB regimens and patient and tumor characteristics. To disentangle these features, we performed a standardized meta-analysis of eight cohorts of patients treated with anti-PD-1 (n=290), anti-CTLA-4 (n=175), and combination anti-PD-1/anti-CTLA-4 (n=51) with RNA sequencing of pre-treatment tumor and clinical annotations. Stratifying by immune-high vs -low tumors, we found that surprisingly, high immune infiltrate was a biomarker for response to combination ICB, but not anti-PD-1 alone. Additionally, hypoxia-related signatures were associated with non-response to anti-PD-1, but only amongst immune infiltrate-high melanomas. In a cohort of scRNA-seq of patients with metastatic melanoma, hypoxia also correlated with immunosuppression and changes in tumor-stromal communication in the tumor microenvironment (TME). Clinically actionable targets of hypoxia signaling were also uniquely expressed across different cell types. We focused on one such target, HIF-2

Indexed as

anti-PD-1HIF-2αhypoxiaimmunotherapymelanoma

Identifiers

PMID39554029
PMCPMC11565796

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.