Protein discovered that limits body’s ability to fight cancer

A protein called Meteorin-like (METRNL) in the tumor microenvironment saps energy from T cells, thereby severely limiting their ability to fight cancer, according to new research directed by investigators at the Johns Hopkins University School of Medicine and the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy, reports Science Daily.

Finding ways to block the effects of METRNL signaling on tumor-infiltrating T cells may allow these immune cells to regain the energy necessary to eliminate tumors.

A report about the work was published in the journal Immunity.

METRNL has been described in the medical literature before -- initially as playing a role in helping keep cold or exercising animals (and people) warm by poking holes in the mitochondria (energy factory) of fat cells so they produce heat. However, it had not previously been known to be active in cancer or in T cells, says lead study author Christopher Jackson, M.D., an assistant professor of neurosurgery at Johns Hopkins.

When T cells try to eliminate a tumor, the state of chronic stimulation/stress causes them to secrete METRNL, Jackson explains.

Once METRNL is secreted, it interacts with the mitochondria and pokes holes in the electron transport chain, a cluster of proteins participating in a process to create energy.

When T cells can no longer keep up with their energy requirements, they stop trying to kill cancer cells, which enables cancer cells to multiply and spread.

During the study, researchers observed that METRNL is activated through a family of transcription factors (proteins that control the rate of transcription of genetic information from DNA to RNA) called E2F, that it is dependent on signaling by a receptor called PPAR delta, and that modulating these factors downstream can block the effects of METRNL.

"Others have shown that metabolic dysfunction limits T cells' ability to fight cancer, but we are among the first to describe a discrete signaling pathway that causes that to happen," Jackson says.

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