The protein behind immunotherapy resistance
Immunotherapy is a cutting-edge approach to treating cancer by turning the patient’s own immune system against their tumor. Our increasing knowledge of the mechanisms by which the body regulates immune responses has been transformative to our fight against cancer.
But despite success rates, immunotherapy has time and again met with a stubborn obstacle: tumor cells often evade the “radar” of immune cells seeking to destroy them. This in turn leads to treatment resistance, which in many cases would benefit from a deeper understanding of mechanisms that can help circumvent it.
A new study led by scientists at EPFL has now uncovered a protein that plays a key role in helping tumors evade immune destruction. The protein, named “fragile X mental retardation protein” (FMRP), regulates a network of genes and cells in the tumor microenvironment that contribute to its ability to “hide” from immune cells. Normally, FMRP is involved in regulating protein translation and the stability of mRNA in neurons. But the researchers found that it is aberrantly up-regulated in multiple forms of cancer.
The study, published in Science, was led by researchers in the group of Douglas Hanahan at the Swiss Institute for Experimental Cancer Research (ISREC) and the Lausanne Branch of the Ludwig Institute for Cancer Research, along with colleagues from the University Hospital of Lausanne (CHUV) and other Swiss institutions. The discovery has also led to an EPFL spin-off, Opna Bio, whose staff were also involved in the research.
But why FMRP? The idea came from previous studies showing that cancer cells that naturally overexpress FMRP are invasive and metastatic. Other studies show that if, in contrast, FMRP fails to be expressed in developing neurons it can lead to cognitive defects (hence the “mental retardation” part of the protein’s name).
With this evidence in mind, the researchers set off to investigate the expression of FMRP in human tumors. They then assessed its tumor-promoting functions in mouse models of cancer, and finally studied its association with prognosis for human cancer patients.
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