AgingResearch.NewsJoin free
bioRxiv

Blood-cell mutations had opposite effects on breast tumors in mice

As mice aged, mutations in the Dnmt3a gene prevented breast cancer progression, while mutations in the Tet2 gene drove it.

Paper by Nagihan G. Gonullu, Karolina A. Zielińska, Jonas Fullin, +3 more authorsMarkus Gabriel Manz · University Hospital Zurich and University of Zurich
Breast tissue contains a dense tumor and a fragmented tumor surrounded by more immune cells, with small laboratory mice nearby.

Our read

Mechanisms
Studied:
Preprint: experiments in mice with engineered blood-cell mutations
What changed:
In aging mice, Dnmt3a-mutant blood cells prevented breast cancer progression, while Tet2-mutant blood cells drove it
The catch:
Progression of naturally arising breast tumors was not measured; tumors were implanted

Editor of record: Boris Djordjevic · AgingResearch.News

Paper
Follow @agingbrief

Mice engineered to develop mutations in either the Dnmt3a or Tet2 gene in blood cells received breast cancer cells from genetically matched mice in animal experiments. The experiments modeled clonal hematopoiesis, the expansion of groups of blood cells carrying acquired mutations.

As the mice aged, Dnmt3a-mutant blood cells prevented breast cancer progression, while Tet2-mutant blood cells drove it. In the Dnmt3a model, macrophages, a type of immune cell within tumors, supported cancer-killing immune cells called T cells. In the Tet2 model, macrophages instead took on an inflammatory state that suppressed immune defenses. Blocking inflammation-related signals reduced tumor progression in aged Tet2-mutant mice and partly restored immune activity against tumors.

Why it matters

The age-related expansion of mutated blood cells is linked to worse outcomes in people with cancer. The authors identify inflammation linked to Tet2-mutant blood cells as a possible therapeutic target.

Caveats

Engineered blood-cell mutations and implanted mouse tumors leave open whether the same opposing effects occur in people with naturally arising mutations. The findings come from a preprint that has not been peer-reviewed.

Where the evidence stands

Il-1r1 blockade

Mice: a single group. Cells, worms or flies and humans: nothing yet.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

  • 2 independent labs in 1 country
  • Funders: Fondation Brain Canada and 5 more
  • 1 of 2 findings with company ties

DNMT3A

Mice and humans: replicated by independent labs. Cells: a single group. Worms or flies: nothing yet.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

No results posted: trials that ended over a year ago with no results on ClinicalTrials.gov and no paper reporting them.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 44 independent labs in 15 countries
  • 1 finding against
  • 22 trials, 4 with no results posted
  • Funders: National Cancer Institute and others
  • 19 of 78 findings with company ties
  • 6 of 22 trials sponsored by developers of drugs aimed at it

Comments

Be the first to comment.

More on DNMT3A