Evidence map›Paper›PMID 34235080›Full record

ReviewFrontiers in oncology2021

How to Better Understand the Influence of Host Genetics on Developing an Effective Immune Response to Thoracic Cancers.

Kiarash Behrouzfar, Kimberley Burton, Steve E Mutsaers, Grant Morahan, Richard A Lake, Scott A Fisher

Open access · goldAbstract readReview
In one paragraph

Review in Frontiers in oncology, 2021. 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
0.4field-weighted citation impact, top 38% 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
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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

6 authors at 3 institutions in 1 country.

Kiarash BehrouzfarNational Centre for Asbestos Related Diseases (NCARD), University of Western Australia, Nedlands, WA, Australia.
Kimberley BurtonNational Centre for Asbestos Related Diseases (NCARD), University of Western Australia, Nedlands, WA, Australia.
Steve E MutsaersSchool of Biomedical Sciences, University of Western Australia, Nedlands, WA, Australia.
Grant MorahanCentre for Diabetes Research, Harry Perkins Institute of Medical Research, Nedlands, WA, Australia.
Richard A LakeNational Centre for Asbestos Related Diseases (NCARD), University of Western Australia, Nedlands, WA, Australia.
Scott A FisherNational Centre for Asbestos Related Diseases (NCARD), University of Western Australia, Nedlands, WA, Australia.
Asbestos Diseases Research Institute · AUHarry Perkins Institute of Medical Research · AUUniversity of Western Australia · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Thoracic cancers pose a significant global health burden. Immune checkpoint blockade therapies have improved treatment outcomes, but durable responses remain limited. Understanding how the host immune system interacts with a developing tumor is essential for the rational development of improved treatments for thoracic malignancies. Recent technical advances have improved our understanding of the mutational burden of cancer cells and changes in cancer-specific gene expression, providing a detailed understanding of the complex biology underpinning tumor-host interactions. While there has been much focus on the genetic alterations associated with cancer cells and how they may impact treatment outcomes, how host genetics affects cancer development is also critical and will greatly determine treatment response. Genome-wide association studies (GWAS) have identified genetic variants associated with cancer predisposition. This approach has successfully identified host genetic risk factors associated with common thoracic cancers like lung cancer, but is less effective for rare cancers like malignant mesothelioma. To assess how host genetics impacts rare thoracic cancers, we used the Collaborative Cross (CC); a powerful murine genetic resource designed to maximize genetic diversity and rapidly identify genes associated with any biological trait. We are using the CC in conjunction with our asbestos-induced MexTAg mouse model, to identify host genes associated with mesothelioma development. Once genes that moderate tumor development and progression are known, human homologues can be identified and human datasets interrogated to validate their association with disease outcome. Furthermore, our CC-MexTAg animal model enables in-depth study of the tumor microenvironment, allowing the correlation of immune cell infiltration and gene expression signatures with disease development. This strategy provides a detailed picture of the underlying biological pathways associated with mesothelioma susceptibility and progression; knowledge that is crucial for the rational development of new diagnostic and therapeutic strategies. Here we discuss the influence of host genetics on developing an effective immune response to thoracic cancers. We highlight current knowledge gaps, and with a focus on mesothelioma, describe the development and application of the CC-MexTAg to overcome limitations and illustrate how the knowledge gained from this unique study will inform the rational design of future treatments of mesothelioma.

Indexed as

Collaborative Crosshost geneticsmesotheliomaMexTAgthoracic malignanciestumor immune microenvironment

Identifiers

PMID34235080
PMCPMC8256168
OpenAlexW3176423860

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.