FMRP mediates immune evasion of mouse tumors

The researchers reported that gene inactivation of neural fragility X intellectual disability protein (FMRP) in cancer cells led to reduced growth and increased
vulnerability of T cells in mouse tumors.
Many human cancers develop the ability to evade the adaptive immune system, making them resistant to immunotherapy
.

Treatment strategies designed to disrupt these immune vulnerability barriers have shown promising results
in some patients and cancers.
However, most patients do not respond to immunotherapy or achieve limited or short-term efficacy
.
These combined results highlight the urgent need to better understand the cellular and molecular mechanisms of cancer immune responses in order to develop more effective treatments
.

To address this need, the researchers investigated the potential role of FMRP, an RNA-binding translation regulator protein commonly associated with
the stability and translation of neuronal RNA.
While previous studies have also shown that FMRP is associated with tumor progression, little is known about its functional role in cancer and immune regulation
.

They genetically regulated the expression of FMRP genes in mouse cancer cells, and found that immune evasion often involves frequent and abnormal expression of FMRP in solid tumors, which has the effect of
inhibiting the immune attack of cancer cells.
Inactivation of FMRP expression in mouse tumor cells leads to reduced tumor growth and greater vulnerability to T cell attack, thereby improving the survival rate
of mice.

The authors suggest that, mechanistically, FMRP creates barriers to the recruitment and expansion of T lymphocytes within tumors, which allows them to evade immune destruction
.
"The widespread expression of FMRP in solid tumors, accompanied by induction of their cancer regulatory network, constitutes a previously unrecognized mechanism that allows tumors to evade immune destruction
," the authors wrote.