Evidence map›Paper›PMID 38345376›Full record

ArticleCancer immunology research2024

Intragenic Rearrangement Burden Associates with Immune Cell Infiltration and Response to Immune Checkpoint Blockade in Cancer.

Han Zhang, Sanghoon Lee, Renee R Muthakana, Binfeng Lu, David N Boone, Daniel Lee, Xiao-Song Wang

Open access · bronzeAbstract read
In one paragraph

Article in Cancer immunology research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.1field-weighted citation impact, top 21% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
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.

Han ZhangUPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.ORCID 0000-0003-3023-4767
Sanghoon LeeUPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.ORCID 0000-0001-8564-2392
Renee R MuthakanaUPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.ORCID 0009-0005-3016-721X
Binfeng LuCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey.ORCID 0009-0003-3293-4086
David N BooneUPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.ORCID 0000-0002-1258-7473
Daniel LeeUPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.ORCID 0000-0003-4411-3595
Xiao-Song WangUPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.ORCID 0000-0002-2570-7139
University of Pittsburgh · USCenter for Discovery · US

Funding

CHARACTERIZATION OF RECURRENT ADJACENT GENE TRANSLOCATIONS IN BREAST CANCERR01CA183976 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WANG, XIAOSONG · 2014 to 2019
$1.6M
Integrative Consig: NLK as Attractive Drug Target for Intractable Breast CancerR01CA181368 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WANG, XIAOSONG · 2014 to 2018
$1.6M
High-Throughput Computing for Genomics and Bioinformatics ResearchS10OD028483 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEE, ADRIAN V · 2021 to 2021
$574k
Characterization of EPHA3 intragenic rearrangements in high-grade serous carcinoma progression and recurrenceR21CA237964 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WANG, XIAOSONG · 2020 to 2021
$402k
NCI NIH HHS R01 CA181368NCI NIH HHS R01 CA183976NCI NIH HHS R21 CA237964NIH HHS S10 OD028483
6 · The paper itself

Abstract

Immune checkpoint blockade (ICB) can induce durable cancer remission. However, only a small subset of patients gains benefits. While tumor mutation burden (TMB) differentiates responders from nonresponders in some cases, it is a weak predictor in tumor types with low mutation rates. Thus, there is an unmet need to discover a new class of genetic aberrations that predict ICB responses in these tumor types. Here, we report analyses of pan-cancer whole genomes which revealed that intragenic rearrangement (IGR) burden is significantly associated with immune infiltration in breast, ovarian, esophageal, and endometrial cancers, particularly with increased M1 macrophage and CD8+ T-cell signatures. Multivariate regression against spatially counted tumor-infiltrating lymphocytes in breast, endometrial, and ovarian cancers suggested that IGR burden is a more influential covariate than other genetic aberrations in these cancers. In the MEDI4736 trial evaluating durvalumab in esophageal adenocarcinoma, IGR burden correlated with patient benefits. In the IMVigor210 trial evaluating atezolizumab in urothelial carcinoma, IGR burden increased with platinum exposure and predicted patient benefit among TMB-low, platinum-exposed tumors. Altogether, we have demonstrated that IGR burden correlates with T-cell inflammation and predicts ICB benefit in TMB-low, IGR-dominant tumors, and in platinum-exposed tumors.

Indexed as

Carcinoma, Transitional CellUrinary Bladder NeoplasmsBiomarkers, TumorFemaleHumansImmune Checkpoint InhibitorsMutationPlatinumBiomarkers, TumorImmune Checkpoint InhibitorsPlatinum

Identifiers

PMID38345376
PMCPMC11107381
OpenAlexW4391745464

What OpenQuestion holds

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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.